Patel, Komal; Patel, Amit; Dave, Jayant; Patel, Chaganbhai
The present manuscript describes simple, sensitive, rapid, accurate, precise and economical spectrophotometric method for the simultaneous determination of telmisartan and metoprolol succinate in combined tablet dosage form. The method is based on the absorbance correction equations for analysis of both the drugs using methanol as solvent. Telmisartan has absorbance maxima at 296 nm and metoprolol succinate has absorbance maxima at 223 nm in methanol. The linearity was obtained in the concentration range of 2-16 μg/ ml and 3-24 μg/ml for telmisartan and metoprolol succinate, respectively. The concentrations of the drugs were determined by using absorbance correction method at both the wavelengths. The method was successfully applied to pharmaceutical dosage form because no interference from the tablet excipients was found. The suitability of this method for the quantitative determination of telmisartan and metoprolol succinate was proved by validation. The proposed method was found to be simple and sensitive for the quality control application of telmisartan and metoprolol succinate in pharmaceutical dosage form. The result of analysis has been validated statistically and by recovery studies. Recoveries were found in the range of 98.08-100.55% of telmisartan and 98.41-101.87% of metoprolol succinate.
Patel Satish A; Patel Paresh U; Patel Natavarlal J.
The manuscript describes validated absorbance correction method for the estimation of nebivolol and amlodipine besylate in combined dosage form. Absorbance correction method was based on property of additivity of absorbances. The two wavelengths on amlodipine besylate curve were found out where it showed same absorbance, which were 262 and 332.5 nm. At 332.5 nm, amlodipine besylate showed some absorbance while nebivolol showed zero absorbance. Both the drugs gave absorbance at 262 nm. The met...
Saxena Vaibhav; Khinchi Mahaveer Pr; Gupta M.K.; Agarwal Dilip; Sharma Natasha
Orally disintegrating tablets (ODTs) have emerged as one of the popular and widely accepted dosage forms, especially for the paediatric and geriatric patients. In recent decades, a variety of pharmaceutical research has been conducted to develop new dosage forms. Among the dosage forms developed to facilitate ease of medication, the rapid disintegrating tablet (RDT) is one of the most widely employed commercial products.1 As our society is becoming increasingly aged, the development of Fast-...
Full Text Available A new reverse phase high performance liquid chromatography (RP-HPLC method has been developed for the simultaneous estimation of gemcitabine hydrochloride and capecitabine hydrochloride in combined tablet dosage form. An inertsil ODS-3 C-18 column having dimensions of 250×4.6 mm and particle size of 5 µm, with mobile phase containing a mixture of acetonitrile : water : triethyelamine in the ratio of (70 : 28 : 2v/v was used. The pH of mobile phase was adjusted to 4.0 with ortho-phosphoric acid. The flow rate was 1 mL/min and the column effluents were monitored at 260 nm. The retention time for gemcitabine hydrochloride and capecitabine hydrochloride was found to be 2.76 and 2.3 min respectively. The proposed method was validated in terms of linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. The method was found to be linear in the range of 10-50 µg/mL and 4-24 µg/mL for gemcitabine hydrochloride and capecitabine hydrochloride, with regression coefficient r = 0.999 and r = 0.999, respectively.
Purpose: To develop and validate simple, rapid and sensitive spectrophotometric procedures for determination of trimipramine in tablet dosage form. Methods: The methods were based on the interaction of trimipramine as n-electron donor with the ο-acceptor, iodine and various π-acceptors, namely: chloranil (CH), ...
Formulation development and evaluation of fast disintegrating tablets of salbutamol sulphate, cetirizine hydrochloride in combined pharmaceutical dosage form: a new era in novel drug delivery for pediatrics and geriatrics.
Sharma, Deepak; Singh, Gurmeet; Kumar, Dinesh; Singh, Mankaran
The objective of the present study was to prepare the fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form for respiratory disorders such as bronchitis, asthma, and coughing for pediatrics and geriatrics. The tablets were prepared by direct compression technique. Superdisintegrant such as Sodium Starch Glycolate was optimized as 4% on the basis of least disintegration time. Different binders such as MCC and PVP K-30 were optimized along with optimized superdisintegrant concentration. 1% MCC was selected as optimum binder concentration on the basis of least disintegration time. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time, and drug content uniformity. Optimized formulation was further evaluated by in vitro dissolution test, drug-excipient compatibility, and accelerated stability study. Percent weight variation and content uniformity were within the acceptable limit. The friability was less than 1%. The wetting time and disintegration time were practically good for all formulations. FTIR studies and accelerated stability study showed that there was no interaction between the drug and excipients. It was concluded that, by employing commonly available pharmaceutical excipients such as superdisintegrants, hydrophilic and swellable excipients and proper filler, a fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form, were formulated successfully with desired characteristics.
Purpose: To develop simple, rapid and selective spectrophotometric methods for the determination of cilostazol in tablet dosage form. Methods: Cilostazol was dissolved in 50 % methanol and its absorbance was scanned by ultraviolet. (UV) spectrophotometry. Both linear regression equation and standard absorptivity were ...
The present study was aimed at formulating and evaluating tablet dosage form of Hunteria umbellata (HU) seed aqueous and purified extracts. HU seeds were dried, pulverized and the powder macerated in water to obtain aqueous extract, while alkaloidal extraction process was used to obtain purified extract. Extracts ...
The results of cilostazol tablet determination by linear regression equation and standard absorptivity methods indicate purity of 100.0 - 102.4 and 98.7 - 101.1 % with ... Conclusion: These validated methods may be useful for routine analysis of cilostazol as bulk drugs, in dosage forms as well as in dissolution studies in the ...
Development and Validation of Stability-Indicating RP-UPLC Method for Simultaneous Determination of Related Substances of S(−Amlodipine and S(−Metoprolol Succinate in Fixed Dose Combination Tablet Dosage Form
Full Text Available A novel, rapid, accurate, sensitive, precise, and stability-indicating reverse-phase ultra-performance liquid chromatographic (RP-UPLC method was developed and validated for determination of related substances of S(−Amlodipine and S(−Metoprolol Succinate in fixed dose combination tablet dosage form. The chromatographic separation was achieved with the use of Acquity UPLC HSS T3, 1.8 μm, 2.1 × 100 mm analytical column at 45°C employing a gradient elution. Mobile phase consisting of mobile phase-A (solution containing 5.0 gm of sodium dihydrogen phosphate monohydrate per liter of water and Acetonitrile in the ratio of 95 : 5 and mobile phase-B (Acetonitrile was used at a flow rate of 0.5 mL min−1 with injection volume of 10 μL and the detection was done at 232 nm using UV detector. The retention times of S(−Metoprolol Succinate and S(−Amlodipine were found to be 2.8 minutes and 8.1 minutes, respectively. During method validation all the parameters were evaluated as per ICH guidelines, which remained well within acceptable limits. This method can be used for the estimation of related substances of S(−Amlodipine and S(−Metoprolol Succinate in fixed dose combination tablet dosage form.
C. K. Rameesa
Full Text Available Background: The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug delivery system as they have improved patient compliance and have some additional advantages compared to other formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to superdisintegrants in the formulation. Thus this type of drug delivery helps a proper per oral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method is the direct compression method. Other special methods are Freeze Drying,Tablet Molding, Sublimation, Spray Drying, Mass extrusion, Phase transition process, etc. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test and dissolution test.
Spectrophotometric simultaneous determination of Tenofovir disoproxil fumarate and Emtricitabine in combined tablet dosage form by ratio derivative, first order derivative and absorbance corrected methods and its application to dissolution study.
Choudhari, Vishnu P; Ingale, Snehal; Gite, Sacchidanand R; Tajane, Dipali D; Modak, Vikram G; Ambekar, Archana
Three simple, economical, precise, and accurate methods are described for the simultaneous determination of Tenofovir disoproxil fumarate (TE) and Emtricitabine (EM) in combined tablet dosage form. The first method is ratio derivative spectra, second is first-order derivative spectrophotometry and third is absorption corrected method. The amplitudes at 271.07 and 302.17 nm in the ratio derivative method, 224.38 and 306.88 nm in the first order derivative method were selected to determine Tenofovir disoproxil fumarate (TE) and Emtricitabine (EM), respectively, in combined formulation. Beer's law is obeyed in the concentration range of 3-21 μg/ml for TE and 2-14 μg/ml for EM for first two methods and range for third method was 6-30 μg/ml of TE and 4-20 μg/ml of EM. The percent assay for commercial formulation was found to be in the range 98.91%-101.72% for both the analytes by the proposed three methods. Absorption corrected method was successfully applied to carry out dissolution study of commercial tablet formulation by using USP II dissolution test apparatus. The methods were validated with respect to linearity, precision, and accuracy. Recoveries by proposed methods were found in the range of 99.06 %-101.34 % for both the analytes.
Ozkan, Y; Ozalp, Y; Savaşer, A; Ozkan, S A
Dissolution can best be described as a tool that can provide valuable information about the availability of a drug product. In this study, nine different paracetamol tablet dosage forms available on the Turkish Drug Market have been investigated and physical controls were realized. Paddle and rotating basket apparatus methods were applied to all the formulations. In order to evaluate the dissolution rates, five different kinetics have been studied and the best fitting kinetics was found to be the Hixson-Crowell kinetics. It was found that all the preparations are in accordance with the Pharmacopeia standards.
Shete, A S; Yadav, A V; Murthy, M S
The objective of present investigation was to evaluate performance of cocrystals of Mefloquine Hydrochloride (MFL) in tablet dosage form. Our previous investigation showed significant effect of cocrystal formers on improving the solubility and dissolution rate of Mefloquine hydrochloride by cocrystallization method when prepared by solution cocrystallization method. Prepared cocrystals of MFL with different ratio of cocrystal formers were incorporated in tablet dosage form and evaluated for micrometric properties, drug content, hardness, disintegration test, vitro dissolution studies and stability studies. Performance was compared with laboratory prepared tablet of MFL 250 mg. The considerable improvement in the dissolution rate was observed in case of cocrystals based tablets than pure MFL tablets. So we can incorporate cocrystals in tablet dosage form to enhance in vitro and in vivo performance. To the best of our knowledge, this is the first report, cocrystals has been evaluated in tablet dosage form.
Gowekar, N M; Pande, V V; Kasture, A V; Tekade, A R; Chandorkar, J G
Fixed dose combination tablets containing ambroxol HCl and cetirizine HCl are clinically used as mucolytic and antiallergic. Several spectrophotometric and HPLC methods have been reported for simultaneous estimation of these drugs with other drugs. The drugs individually and in mixture obeys Beer's law over conc. range 1.2-4.4 microg/mL for cetirizine HCL and for ambroxol HCL 15-52 microg/mL at all five sampling wavelengths (correlation coeff. well above 0.995). The mean recoveries from tablet by standard addition method were 100.18% (+/-2.4) and 100.66 % (+/-2.31). The present work reports simple, accurate and precise spectrophotometric methods for their simultaneous estimation from tablet dosage form.
J. Adlin Jino Nesalin
Full Text Available Two simple spectrophotometric methods have been developed for the estimation of tadalafil in both pure and tablet dosage form. Methods A and B are based on the formation of ion-pair complexes of the drug with dyes such as bromothymol blue (BTB and bromocresol green (BCG in acidic buffer solution followed by their extraction with chloroform to form yellow colored chromogen with absorption maxima at 420 nm and 415 nm respectively. Beer’s law is valid in the concentration range of 10-50 mcg/mL for both the methods. These developed methods were validated for precision, accuracy, ruggedness and robustness. Statistical analysis proves that the methods are reproducible and selective for the routine analysis of the said drug.
determination by linear regression equation and standard absorptivity methods indicate purity ... Keywords: Cilostazol tablets, UV spectrophotometry, Linear regression equation, Standard absorptivity. .... The validated methods were applied to.
Lal, Manjari; Lai, Manshun; Estrada, Marcus; Zhu, Changcheng
Current presentations of the anti-HIV drugs lopinavir and ritonavir make appropriate dosing for children difficult. We conducted a feasibility study to develop a formulation for these drugs with child-safe excipients in a flexible dosage form for children across the pediatric age spectrum. The freeze-drying in blister approach was used to produce fast-dissolving tablets (FDTs), as these can be dispersed in fluids for easy administration, even to infants, and appropriate portions of the dispersion can be given for different ages/weights. We combined various ratios of polymers, surfactants, and bulking agents to incorporate the 2 highly hydrophobic drugs while maintaining drug stability, rapid disintegration, and good handling properties. The final FDT was robust and disintegrated in 0.5 mL of fluid in 10 s with up to 4 tablets dissolving in 2 mL to achieve varying doses accommodated in a common teaspoon. Drug recovery after dissolution in small volumes of liquid or fluid foods was 90%-105%. The final candidate FDT was stable at 40°C, 75% relative humidity for up to 3 months. FDTs are a promising flexible dosage form for antiretroviral treatment for pediatric patients, especially in low-resource settings. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Rodenhuis, N.; Smet, P.A.G.M. de; Barends, D.M.
The aim of the study was to get insight into the rationale of scored tablets. This was pursued by studying patient's reasons for subdividing ("breaking") scored and unscored tablets. Patients who picked up their prescriptions in 5 community pharmacies in The Netherlands were questioned. Two-hundred
Rote, Ambadas R; Bhalerao, Swapnil R
To develop and validate a simple, precise and accurate spectrophotometric method for the simultaneous estimation of nabumetone and paracetamol in their combined tablet dosage form. This method is based on first-order derivative spectroscopy. For determination of sampling wavelengths, each of nabumetone and paracetamol were scanned in the wavelength range of 200-400 nm in the spectrum mode and sampling wavelengths were selected at 261 nm (zero crossing of nabumetone) where paracetamol showed considerable absorbance and at 248.2 nm (zero crossing of paracetamol) where nabumetone showed considerable absorbance. Beer's law obeyed in the concentration range of 3-18 μg/ml for both the drugs. The correlation coefficients were found to be 0.9992 and 0.9998 for nabumetone and paracetamol, respectively. Mean recoveries were found satisfactory. The proposed method can be successfully applied for simultaneous estimation of nabumetone and paracetomol.
Raza, Asad; Ansari, Tariq Mahmood
A fast, sensitive and extraction free spectrophotometric method for the quantitative determination of citalopram hydrobromide in pharmaceutical raw and tablet formulations has been proposed. The newly proposed method is based on the charge transfer reaction between citalopram as electron donor and chloranil as electron acceptor. The charge transfer complex of citalopram and chloranil shows λ(max) at 550 nm in methanol. The experimental conditions such as reaction time, temperature, stoichiometry of the colored complex have been optimized. The developed method allows the determination of citalopram hydrobromide over a concentration range of 1-25 mg/ ml. The proposed method is used to determine the citalopram in tablet dosage forms. The results of proposed method are compared to the official USP method. The newly developed method is accurate, reproducible and easy to perform. It does not require stringent experimental conditions. No interference has been observed for excipients and additives in tablet formulations.
Sivadas, Akhila; Sathi, Aiswarya; Sathi, Kavya; Rahate, Kalpana Pravin
Citicoline (CN) and piracetam (PM) combination in tablet formulation is newly introduced in market. It is necessary to develop suitable quality control methods for rapid and accurate determination of these drugs. The study aimed to develop the methods for simultaneous determination of CN and PM in combined dosage form. The first method was developed by formation and solving simultaneous equations using 280.3 and 264.1 nm as two analytical wavelengths. Second method was absorbance ratio in which wavelengths selected were 256.6 nm as its absorptive point and 280.3 nm as λmax of CN. According to International Conference on Harmonization (ICH) norm, the parameters - linearity, precision, and accuracy were studied. The methods were validated statistically and by recovery studies. Both the drugs obeyed Beer-Lambert's law at the selected wavelengths in concentration range of 5-13 μg/ml for CN and 10-22 μg/ml for PM. The percentage of CN and PM in marketed tablet formulation was found to be 99.006 ± 0.173 and 99.257 ± 0.613, respectively; by simultaneous equation method. For Q-Absorption ratio method the percentage of CN and PM was found to be 99.078 ± 0.158 and 99.708 ± 0.838, respectively. The proposed methods were simple, reproducible, precise and robust. The methods can be successfully applied for routine analysis of tablets.
Bojanapu, A; Subramaniam, A T; Munusamy, J; Dhanapal, K; Chennakesavalu, J; Sellappan, M; Jayaprakash, V
A novel, precise, rapid and sensitive reverse phase high performance liquid chromatographic method has been developed for the validated estimation of Tadalafil in bulk and tablet dosage form. The separation was achieved on Agilent Eclipse XDB C18 column (150 mm×4.6 mm, 5 µ) using a mobile phase that consists of the buffer (potassium dihydrogen orthophosphate) and acetonitrile in the ration of 50:50 V/V, pH 6 was adjusted with orthophosphoric acid. The flow rate was maintained at 1.2 ml/min and the detection wavelength was 285 nm. The method was validated for linearity, specificity, sensitivity as per ICH guidelines. The retention time was found to be 3.181 for Tadalafil. The calibration curve was linear over the concentration range of 10-150 µg/ml. The % RSD was satisfactory which showed the method found to be reliable. The high percentage recovery confirmed the suitability of the method for estimation of Tadalafil in pharmaceutical dosage form. The developed method could be applicable for routine analysis of Tadalafil in bulk and tablet dosage form. © Georg Thieme Verlag KG Stuttgart · New York.
Full Text Available A simple, specific, precise, and accurate reversed-phase HPLC method was developed and validated for simultaneous estimation of aspirin and esomeprazole magnesium in tablet dosage forms. The separation was achieved by HyperChrom ODS-BP C18 column (200 mm × 4.6 mm; 5.0 μm using acetonitrile: methanol: 0.05 M phosphate buffer at pH 3 adjusted with orthophosphoric acid (25 : 25 : 50, v/v as eluent, at a flow rate of 1 mL/min. Detection was carried out at wavelength 230 nm. The retention times of aspirin and esomeprazole magnesium were 4.29 min and 6.09 min, respectively. The linearity was established over the concentration ranges of 10–70 μg/mL and 10–30 μg/mL with correlation coefficients (r2 0.9986 and 0.9973 for aspirin and esomeprazole magnesium, respectively. The mean recoveries were found to be in the ranges of 99.80–100.57% and 99.70–100.83% for aspirin and esomeprazole magnesium, respectively. The proposed method has been validated as per ICH guidelines and successfully applied to the estimation of aspirin and esomeprazole magnesium in their combined tablet dosage form.
Patel, Sejal K.; Patel, N. J.
A binary mixture of trifluoperazine HCl and chlordiazepoxide was determined using reversed-phase liquid chromatography method using methanol:water (97:03, v/v) pumped at a flow rate of 1.0 ml/min. Quantification was achieved with ultraviolet detection at 262 nm over concentration ranges of 0.1-1 and 0.5-5 μg/ml; mean accuracies were 101.05±0.47 and 98.97±0.33 %, respectively. The method was successively applied to tablet dosage forms as no chromatographic interferences from the tablet excipients were observed. The method retained its accuracy and precision when the standard addition technique was applied. PMID:20502574
Kumar, D. Anantha; Rao, G. Srinivasa; Rao, J. V. L. N. Seshagiri
A simple, accurate and reproducible RP-HPLC method has been developed for the simultaneous determination of lamivudine, zidovudine and abacavir in tablet dosage forms. Chromatography was carried out on a HiQ Sil C 18 V column using a mobile phase consisting of 0.01 M potassium dihydrogen ortho-phosphate (pH 3.0) and methanol (55:45 v/v) at a flow rate of 0.8 mL/min. The detection was made at 272 nm and stavudine was used as the internal standard for this study. The retention times for lamivud...
A. R. Rote
Full Text Available Three new simple, economic spectrophotometric methods were developed and validated for the estimation of nabumetone in bulk and tablet dosage form. First method includes determination of nabumetone at absorption maxima 330 nm, second method applied was area under curve for analysis of nabumetone in the wavelength range of 326-334 nm and third method was First order derivative spectra with scaling factor 4. Beer law obeyed in the concentration range of 10-30 μg/mL for all three methods. The correlation coefficients were found to be 0.9997, 0.9998 and 0.9998 by absorption maxima, area under curve and first order derivative spectra. Results of analysis were validated statistically and by performing recovery studies. The mean percent recoveries were found satisfactory for all three methods. The developed methods were also compared statistically using one way ANOVA. The proposed methods have been successfully applied for the estimation of nabumetone in bulk and pharmaceutical tablet dosage form.
Thiruvengada, Rajan Vs; Mohamed, Saleem Ts; Ramkanth, S; Alagusundaram, M; Ganaprakash, K; Madhusudhana, Chetty C
An isocratic reversed phase high-performance liquid chromatographic method with ultraviolet detection at 220 nm has been developed for the quantification of itopride hydrochloride in tablet dosage form. The quantification was carried out using C(8) column (250 mm × 4.6 mm), 5-μm particle size SS column. The mobile phase comprised of two solvents (Solvent A: buffer 1.4 mL ortho-phosphoric acid adjusted to pH 3.0 with triethyl amine and Solvent B: acetonitrile). The ratio of Solvent A: Solvent B was 75:25 v/v. The flow rate was 1.0 mL (-1)with UV detection at 220 nm. The method has been validated and proved to be robust. The calibration curve was linear in the concentration range of 80-120% with coefficient of correlation 0.9995. The percentage recovery for itopride HCl was 100.01%. The proposed method was validated for its selectivity, linearity, accuracy, and precision. The method was found to be suitable for the quality control of itopride HCl in tablet dosage formulation.
Full Text Available Context: Citicoline (CN and piracetam (PM combination in tablet formulation is newly introduced in market. It is necessary to develop suitable quality control methods for rapid and accurate determination of these drugs. Aim: The study aimed to develop the methods for simultaneous determination of CN and PM in combined dosage form. Materials and Methods: The first method was developed by formation and solving simultaneous equations using 280.3 and 264.1 nm as two analytical wavelengths. Second method was absorbance ratio in which wavelengths selected were 256.6 nm as its absorptive point and 280.3 nm as λmax of CN. According to International Conference on Harmonization (ICH norm, the parameters - linearity, precision, and accuracy were studied. The methods were validated statistically and by recovery studies. Results: Both the drugs obeyed Beer-Lambert′s law at the selected wavelengths in concentration range of 5-13 μg/ml for CN and 10-22 μg/ml for PM. The percentage of CN and PM in marketed tablet formulation was found to be 99.006 ± 0.173 and 99.257 ± 0.613, respectively; by simultaneous equation method. For Q-Absorption ratio method the percentage of CN and PM was found to be 99.078 ± 0.158 and 99.708 ± 0.838, respectively. Conclusions: The proposed methods were simple, reproducible, precise and robust. The methods can be successfully applied for routine analysis of tablets.
Full Text Available Two accurate, precise, sensitve and economical procedures for simultaneous estimation of cetrizine and dextromethorphan in tablet dosage forms have been developed. First method employs formation and solving of simultaneous equations using 230 nm and 280 nm as two analytical wavelengths for both drugs in methanol. The second method is Q-analysis based on measurement of absorptivity at 224 nm (as isobestic point and 280 nm (λmax of CTZ. Cetrizine and dextromethorphan at their respective λmax 280 nm and 230 nm and at 224 nm (isobestic point shows linearity in a concentration range of 10-30 mcg/mL for both the drugs. The recovery studies confirmed accuracy of the proposed methods and low values of standard deviation confirmed precision of the methods. The methods were validated as per ICH guidelines.
Wahdan, Tarek; El-Ghany, Nadia Abd
A differential pulse voltammetric method was described for the determination of domperidone. The method was based on the anodic oxidation of domperidone on a glassy carbon electrode at +0.64 V vs. SCE in Britton-Robinson buffer solution of pH 2.3. The reversibility of the oxidation was tested by cyclic voltammetry; the electrode process is irreversible and diffusion-adsorption controlled. Calibrations are linear over the range 1.0 x 10(-6)-2.0 x 10(-5) M of domperidone with a detection limit of 4.0 x 10(-7) M. The method was applied, without any interference from the excipients, to the determination of the drug in a tablet dosage form.
Sérgio Luiz Dalmora
Full Text Available A dissolution test for in vitro evaluation of tablet dosage forms containing 10 mg of rupatadine was developed and validated by RP-LC. A discriminatory dissolution method was established using apparatus paddle at a stirring rate of 50 rpm with 900 mL of deaerated 0.01 M hydrochloric acid. The proposed method was validated yielding acceptable results for the parameters evaluated, and was applied for the quality control analysis of rupatadine tablets, and to evaluate the formulation during an accelerated stability study. Moreover, quantitative analyses were also performed, to compare the applicability of the RP-LC and the LC-MS/MS methods.
Induri, Madhusudhanareddy; Mantripragada, Bhagavan Raju; Yejella, Rajendra Prasad; Kunda, Pavankumar Reddy; Nannapaneni, Dharma Theja; Boddu, Rajkumar
Two simple and inexpensive UV spectrophotometric methods were developed for the quantification and dissolution studies of meloxicam in tablet dosage forms. Meloxicam was estimated at 365nm and 360nm in Method I and Method II, respectively. The calibration curve was linear over a concentration range from 2.0 to 12.0μg/ml for both methods. The limit of detection and limit of quantitation were found to be 0.12μg/ml and 0.38μg/ml, 0.09μg/ml and 0.27μg/ml for Method I and Method II, respectively. The percentage recoveries of meloxicam were found to be 99.68 to 100.61% and 99.11 to 100.96% for Method I and Method II, respectively. It was concluded that the developed methods are precise, accurate and were successfully applied for the estimation of meloxicam in pharmaceutical formulations and in vitro dissolution studies.
Full Text Available A Fourier transform infrared derivative spectroscopy (FTIR-DS method has been developed for determining furosemide (FUR in pharmaceutical solid dosage form. The method involves the extraction of FUR from tablets with N,N-dimethylformamide by sonication and direct measurement in liquid phase mode using a reduced path length cell. In general, the spectra were measured in transmission mode and the equipment was configured to collect a spectrum at 4 cm−1 resolution and a 13 s collection time (10 scans co-added. The spectra were collected between 1400 cm−1 and 450 cm−1. Derivative spectroscopy was used for data processing and quantitative measurement using the peak area of the second order spectrum of the major spectral band found at 1165 cm−1 (SO2 stretching of FUR with baseline correction. The method fulfilled most validation requirements in the 2 mg/mL and 20 mg/mL range, with a 0.9998 coefficient of determination obtained by simple calibration model, and a general coefficient of variation <2%. The mean recovery for the proposed assay method resulted within the (100±3% over the 80%–120% range of the target concentration. The results agree with a pharmacopoeial method and, therefore, could be considered interchangeable.
Gallignani, Máximo; Rondón, Rebeca A.; Ovalles, José F.; Brunetto, María R.
A Fourier transform infrared derivative spectroscopy (FTIR-DS) method has been developed for determining furosemide (FUR) in pharmaceutical solid dosage form. The method involves the extraction of FUR from tablets with N,N-dimethylformamide by sonication and direct measurement in liquid phase mode using a reduced path length cell. In general, the spectra were measured in transmission mode and the equipment was configured to collect a spectrum at 4 cm−1 resolution and a 13 s collection time (10 scans co-added). The spectra were collected between 1400 cm−1 and 450 cm−1. Derivative spectroscopy was used for data processing and quantitative measurement using the peak area of the second order spectrum of the major spectral band found at 1165 cm−1 (SO2 stretching of FUR) with baseline correction. The method fulfilled most validation requirements in the 2 mg/mL and 20 mg/mL range, with a 0.9998 coefficient of determination obtained by simple calibration model, and a general coefficient of variation <2%. The mean recovery for the proposed assay method resulted within the (100±3)% over the 80%–120% range of the target concentration. The results agree with a pharmacopoeial method and, therefore, could be considered interchangeable. PMID:26579407
Bates, T R; Sequeria, J A
The purposes of this investigation were to determine and to compare the oral absorption characteristics of micronized griseofulvin (500 mg) after its administration to humans in the form of a corn oil-in-water emulsion containing dispersed drug, an aqueous suspension, and two different commercial tablets (A and B). The four dosage forms were administered in a random crossover fashion to five fasting subjects, and drug absorption was assessed from urinary excretion data for the major metabolite of the antibiotic (6-desmethylgriseofulvin). The drug was most rapidly, uniformly, and completely absorbed from the corn oil-in-water emulsion. As compared to either the aqueous suspension, Tablet A, or Tablet B, three- to fourfold increases in the maximum body levels and a twofold enhancement in the bioavailability of the antibiotic were observed after administration of the emulsion dosage form. A mechanism based on the ability of the linoleic and oleic acids liberated during the digestion of corn oil to inhibit GI motility and stimulate gallbladder evacuation may explain the marked enhancing effect of emulsified corn oil on griseofulvin absorption in humans. This new lipid-in-water emulsion dosage form of micronized griseofulvin appears to offer several clinical advantages in the treatment of fungal infections.
Malewar, Nikhil; Avachat, Makarand; Kulkarni, Shirish; Pokharkar, Varsha
Venlafaxine Hydrochloride (VH) is a highly soluble and highly permeable antidepressant compound. Thus controlling VH release from tablet dosage form over a prolonged period is a challenge. The objective of this work was to study the effect of various barrier layer formulation compositions, its orientations and manufacturing technology on release profile of highly soluble VH. Different barrier compositions and orientations were established on the same extended release formulations of VH using compression as well as film coating technologies. Barrier effectiveness in reducing the VH release was verified through in vitro dissolution studies. The "belly band" portion of the tablets was successfully oriented in different ways to develop bilayer as well as trilayer tablets. The compression technology had substantially reduced the VH release up to 16% in various compositions and orientation as compared to core tablet. The film coating technology had reduced the VH release up to 14% effectively; thereby shifting the dissolution curve to downside. The explored "belly band" portion of the tablets had reduced the VH release substantially. These innovatively created different barrier orientation technologies hold the great promise of commercialization in future.
Fernanda Rodrigues Salazar
Full Text Available Three methods are proposed for the quantitative determination of raloxifene hydrochloride in pharmaceutical dosage form: ultraviolet method (UV high performance liquid chromatography (HPLC and micellar capillary electrophoresis (MEKC. These methods were developed and validated and showed good linearity, precision and accuracy. Also they demonstrated to be specific and robust. The HPLC and MEKC methods were tested in regards to be stability indicating methods and they showed to have this attribute. The UV method used methanol as solvent and optimal wavelength at 284 nm, obeying Lambert-Beer law in these conditions. The chromatographic conditions for the HPLC method included: NST column C18 (250 x 4.6 mm x 5 µm, mobile phase water:acetonitrile:triethylamine (67:33:0,3 v/v, pH 3.5, flow rate 1.0 mL min-1, injection volume 20.0 µl, UV detection 287 nm and analysis temperature 30 °C. The MEKC method was performed on a fused-silica capillary (40 cm effective length x 50 µm i.d. using as background electrolyte 35.0 mmol L-1 borate buffer and 50.0 mmol L-1 anionic detergent sodium dodecyl sulfate (SDS at pH 8.8. The capillary temperature was 32°C, applied voltage 25 kV, UV detection at 280 nm and injection was perfomed at 45 mBar for 4 s, hydrodimanic mode. In this MEKC method, potassium diclofenac (200.0 µg mL-1 was used as internal standard. All these methods were statistically analyzed and demonstrated to be equivalent for quantitative analysis of RLX in tablets and were successfully applied for the determination of the drug.
Hanaa Saleh, Gamal H. Ragab, Mohammed A. Othman
A sensitive, simple, selective and accurate HPLC method was developed and validated for analysis of antiviral drug Daclatasvir (BMS-790052, DCV) in pure form and in tablet dosage form in the presence of its degradation products. The chromatographic separation achieved by isocratic elution on Hypersil BDS C18, 4.6×150 mm, 5µm column at 25˚c. The mobile phase was a mixture of 0.05M Potassium dihydrogen phosphate (pH-4.5) and acetonitrile in ratio of 50:50 (v/v). The injection volume was 10µl. T...
V. Ashok Chakravarthy
Full Text Available The present work was the development of a simple, efficient, and reproducible stability-indicating reverse-phase high performance liquid chromatographic (RP-HPLC method for simultaneous determination enrofloxacin (EFX and its degradation products including ethylenediamine impurity, desfluoro impurity, ciprofloxacin impurity, chloro impurity, fluoroquinolonic acid impurity, and decarboxylated impurity in tablet dosage forms. The separation of EFX and its degradation products in tablets was carried out on Kromasil C-18 (250×4.6 mm, 5 μm column using 0.1% (v/v TEA in 10 mM KH2PO4 (pH 2.5 buffer and methanol by linear gradient program. Flow rate was 1.0 mL min−1 with a column temperature of 35°C and detection wavelength was carried out at 278 nm and 254 nm. The forced degradation studies were performed on EFX tablets under acidic, basic, oxidation, thermal, humidity, and photolytic conditions. The degraded products were well resolved from the main active drug and also from known impurities within 65 minutes. The method was validated in terms of specificity, linearity, LOD, LOQ, accuracy, precision, and robustness as per ICH guidelines. The results obtained from the validation experiments prove that the developed method is a stability-indicating method and suitable for routine analysis.
Taher, M. A.; Asadollahzadeh, H.; Fazelirad, H.
A very simple and sensitive spectrofluorimetric method was developed for the direct determination of losartan in some commercial tablets. The suggested method is based on the linear relationship between 0.1-5.0 μg/ml of losartan and its fluorescence intensity at 400 nm in acidic medium. The detection limit and relative standard deviation (for ten repetitive measurements of 2.0 μg/ml) were obtained as 12.0 ng/ml and 1.35%, respectively. The recommended method was successfully applied for the determination of losartan in three types of commercial tablets from different brands.
Nov 19, 2007 ... A model of multi-unit dose tablets of theophylline (dose, 600 mg) has been designed to give a prompt release dose (200 mg) in the first 1 h and the remaining sustained release ... granules, microcapsules or microparticles of the same drug but of different release profiles. They are normally formulated into a ...
Gohel, M C; Patel, T M; Parikh, R K; Parejiya, P B; Barot, B S; Ramkishan, A
The aim of this investigation was to develop a novel multifunctional co-processed diluent consisting of microcrystalline cellulose (Avicel PH 102), crospovidone (Polyplasdone XL) and polyethylene glycol 4000. Colloidal silicon dioxide and talc were also incorporated as minor components in the diluent to improve tableting properties. Melt granulation was adopted for preparation of co-processed diluent. Percentage of Avicel PH 102, Polyplasdone XL and polyethylene glycol 4000 were selected as independent variables and disintegration time was chosen as a dependent variable in simplex lattice design. The co-processed diluent was characterised for angle of repose, bulk density, tapped density, Carr's index, percentage of fines and dilution potential study. Acetaminophen and metformin were used as poorly compressible model drugs for preparation of tablets. The blend of granules of drug and extra-granular co-processed diluent exhibited better flow as compared to the blend of drug granules and physical mixture of diluents blend. The diluent exhibited satisfactory tableting properties. The tablets exhibited fairly rapid drug release. In conclusion, melt granulation is proposed as a method of preparing co-processed diluent. The concept can be used to bypass patents on excipient manufacturing.
Mantripragada, Murali Krishna V V N; Rao, Sumathi V; Nutulapati, Venugopal V S; Mantena, Bhaskara P V
A simple, rapid, selective and stability indicating reversed phase-ultra performance liquid chromatography method was developed and validated for the simultaneous quantification of process related and degradation impurities present in Atazanavir and Ritonavir tablets. The two proposed drug components and their respective impurities were separated using Acquity BEH C18 (100 mm × 2.1 mm), 1.7 μ column at a flow rate of 0.4 mL/min. Buffer used as Mobile phase-A which consists of 0.01 M monobasic potassium hydrogen phosphate adjusted the pH to 3.6 and acetonitrile is used as organic modifier (mobile phase-B). The detector wavelength of 240 nm was used for quantifying the impurities. Both the drug components along with their impurities were eluted within a runtime of 18 min. The performance of the developed method was checked by validating the method according to the requirements of International Conference on Harmonization for parameters such as specificity, precision, linearity, ruggedness, accuracy, sensitivity (limit of detection (LOD) and limit of quantitation (LOQ)) and robustness. Linearity and range were established from LOQ level to 150% level. Accuracy of the method was demonstrated from LOQ level to 150% level. The developed stability indicating method is capable for determination of impurities of Atazanavir and Ritonavir in combined tablet dosage form as well as individual dosage forms also. The reported method enables lesser solvent consumption and reduces time and cost of the analysis in quality control laboratory. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Kumari, Richa; Dash, P P; Lal, V K; Mishra, A; Murthy, P N
A rapid and sensitive reverse phase RP-HPLC method is proposed for the estimation of tamsulosin hydrochloride in tablets. Tamsulosin hydrochloride was chromatographed on a reverse phase C18 column with a mobile phase consisting of acetonitrile and water in the ratio of 50:50 v/v. The mobile phase was pumped at a flow rate of 1.5 ml/min. The eluents were monitored at 214 nm. The retention time of the drug was 1.7 min. With this method, linearity was observed between area under curve and concentration of tamsulosin hydrochloride in the injected solution, in the range of 5 to 100 μg/ml. The method was found to be applicable for analysis of the drug in tablets. The results were validated statistically.
Patel Satish A; Patel Natavarlal J.
A simple, sensitive, accurate, precise and economical visible spectrophotometric method was developed and validated for the estimation of cephalexin in tablets. The method is based on the reaction of cephalexin with ninhydrin reagent in methanol giving blue color chromogen, which shows maximum absorbance at 576 nm against reagent blank. The chromogen obeyed Beer’s law in the concentration range of 5-60 µg/ml for cephalexin. The results of the analysis have been validated statistically and by ...
A model of multi-unit dose tablets of theophylline (dose, 600 mg) has been designed to give a prompt release dose (200 mg) in the first 1 h and the remaining sustained release dose (400 mg) to be released over 11 h at a first order release rate constant of 0.24 h-1. The prompt release component (A) consisted of ...
Shaik Harum Rasheed
Full Text Available A reversed phase high performance liquid chromatography (RP-HPLC method was developed, validated and used for the quantitative determination of rabeprazole sodium (RP and itopride hydrochloride (IH, from its tablet dosage form. Chromatographic separation was performed on a Phenomenex C18 column (250 mm × 4.6 mm, 5 μm, with a mobile phase comprising of a mixture of 50 mM ammonium acetate buffer and methanol (20:80v/v, pH 4.5 adjusted with acetic acid, at a flow rate of 1.3 mL/min with detection at 286 nm. Separation was completed in less than 10 min. As per International Conference on Harmonization (ICH guidelines the method was validated for linearity, accuracy, precision, limit of quantitation and limit of detection. Linearity of RP was found to be in the range of 37.5-375 μg/mL and IH was found to be in the range of 5-50 μg/mL. The correlation coefficients were 0.9997 and 0.9995 for RB and IH respectively. The accuracy of the developed method was found to be 98.6-100.7 for RP and 99.42 -100.81 for IH. The experiment shows the developed method is free from interference of excipients. It indicates the developed RP-HPLC method is simple, linear, precise and accurate and it can be conveniently adopted for the routine quality control analysis of the tablet dosage form.
Full Text Available This study proposes a percussion learning device that combines tablet computers and robots. This device comprises two systems: a rhythm teaching system, in which users can compose and practice rhythms by using a tablet computer, and a robot performance system. First, teachers compose the rhythm training contents on the tablet computer. Then, the learners practice these percussion exercises by using the tablet computer and a small drum set. The teaching system provides a new and user-friendly score editing interface for composing a rhythm exercise. It also provides a rhythm rating function to facilitate percussion training for children and improve the stability of rhythmic beating. To encourage children to practice percussion exercises, a robotic performance system is used to interact with the children; this system can perform percussion exercises for students to listen to and then help them practice the exercise. This interaction enhances children’s interest and motivation to learn and practice rhythm exercises. The results of experimental course and field trials reveal that the proposed system not only increases students’ interest and efficiency in learning but also helps them in understanding musical rhythms through interaction and composing simple rhythms.
Full Text Available Simple, rapid and accurate new vierordt’s (VI method or simultaneous equation (SE method is developed and validated for the simultaneous estimation of dutasteride (DU and tamsulosin hydrochloride (TA in pure and pharmaceutical dosage form. The method is based on the measurement of absorbance at two wavelengths 240.6 nm and 279.4 nm, λmax of DU and TA in methanol respectively. Calibration curves are linear in the concentration ranges 20–40 μg/ml for DU and 16–32 μg/ml for TA. LOD, LOQ, precision and recovery studies are calculated. The proposed method is successfully applied for simultaneous estimation of DU and TA in pure and pharmaceutical dosage form.
effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form. Keywords: antihistaminic, effervescent tablets, 2-hydroxypropyl-β-cyclodextrin, mannitol, taste masking
Labib, Gihan S
Levocetirizine HCl, a second-generation piperazine derivative and H1-selective antihistaminic agent, possesses few side effects. The first objective of the study was to compare and evaluate the taste-masking effect of different ratios of 2-hydroxypropyl-β-cyclodextrin and mannitol on levocetirizine HCl using an inclusion complex and solid dispersion, respectively. The second objective was to study the possibility of preparing and evaluating effervescent tablets from the best-chosen taste-masked blends for the purpose of their use either as orodispersible tablets or as water-soluble effervescent tablets, according to patients' will. Prepared taste-masked blends were prepared and subjected to palatability, Fourier-transform infrared spectroscopy, and differential scanning calorimetry studies. Tablets containing different percentages of effervescent mixtures were prepared by direct compression on the selected taste-modified blends. Evaluation tests were conducted, including flowability and compressibility on the precompressed blends and hardness, friability, wetting time, effervescent time, in vitro, in vivo disintegration time, and in vitro dissolution study on the compressed tablets. Formulated tablets were evaluated and compared to marketed orodispersible tablets for mouth feel and palatability. All prepared tablets showed convenient physical and palatability properties compared to the selected brand. The in vitro drug-release study revealed fast release of levocetirizine HCl within 5 minutes from all prepared tablets. Levocetirizine HCl effervescent tablets are likely to increase patient compliance with drug administration. Moreover, the use of these effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form.
Labib, Gihan S
Objectives Levocetirizine HCl, a second-generation piperazine derivative and H1-selective antihistaminic agent, possesses few side effects. The first objective of the study was to compare and evaluate the taste-masking effect of different ratios of 2-hydroxypropyl-β-cyclodextrin and mannitol on levocetirizine HCl using an inclusion complex and solid dispersion, respectively. The second objective was to study the possibility of preparing and evaluating effervescent tablets from the best-chosen taste-masked blends for the purpose of their use either as orodispersible tablets or as water-soluble effervescent tablets, according to patients’ will. Materials and methods Prepared taste-masked blends were prepared and subjected to palatability, Fourier-transform infrared spectroscopy, and differential scanning calorimetry studies. Tablets containing different percentages of effervescent mixtures were prepared by direct compression on the selected taste-modified blends. Evaluation tests were conducted, including flowability and compressibility on the precompressed blends and hardness, friability, wetting time, effervescent time, in vitro, in vivo disintegration time, and in vitro dissolution study on the compressed tablets. Formulated tablets were evaluated and compared to marketed orodispersible tablets for mouth feel and palatability. Results All prepared tablets showed convenient physical and palatability properties compared to the selected brand. The in vitro drug-release study revealed fast release of levocetirizine HCl within 5 minutes from all prepared tablets. Conclusion Levocetirizine HCl effervescent tablets are likely to increase patient compliance with drug administration. Moreover, the use of these effervescent tablets in an orodispersible dosage form can improve oral drug bioavailability and act as an attractive pediatric dosage form. PMID:26379426
Suganthi, A; John, Sofiya; Ravi, T K
A simple, precise, sensitive, rapid and reproducible HPTLC method for the simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets was developed and validated. This method involves separation of the components by TLC on precoated silica gel G60F254 plate with solvent system of n-butanol, toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out densitometrically using a UV detector at 288 nm in absorbance mode. This system was found to give compact spots for rabeprazole (Rf value of 0.23 0.02) and for itopride hydrochloride (Rf value of 0.75+/-0.02). Linearity was found to be in the range of 40-200 ng/spot and 300-1500 ng/spot for rabeprazole and itopride hydrochloride. The limit of detection and limit of quantification for rabeprazole were 10 and 20 ng/spot and for itopride hydrochloride were 50 and 100 ng/spot, respectively. The method was found to be beneficial for the routine analysis of combined dosage form.
Dina S. El-Kafrawy
Full Text Available A simple, rapid and selective high performance thin layer chromatography (HPTLC method was developed for the simultaneous determination of cinnarizine (CNZ and dimenhydrinate (DMH in pure form and in their combined dosage form. Reviewing the literature revealed that there are no reports for the use of TLC for the assay of this mixture. Effective separation was achieved using Fluka HPTLC aluminum sheets of silica gel 60 F254 using chloroform–n-hexane–methanol (8.5:0.8:0.7, by volume as mobile phase, followed by densitometric measurement of CNZ and DMH spots at 254 and 279 nm, respectively. The reliability and analytical performance of the proposed HPTLC method were statistically validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness and detection and quantification limits. Calibration curves were linear in the ranges of 50–400 and 50–500 ng/spot for CNZ and DMH, respectively with correlation coefficients >0.9998. The limits of detection were 8.1 and 8.0 ng/spot for CNZ and DMH respectively. The validated HPTLC method was applied to the simultaneous analysis of CNZ and DMH in laboratory-prepared tablets. Both analytes were successfully quantified with good recovery values, and no interference was encountered from the inactive ingredients.
Full Text Available Objective : Telmisartan is a potent, long-lasting, nonpeptide antagonist of the angiotensin II type-1 (AT 1 receptor that is indicated for the treatment of essential hypertension. Hydrochlorothiazide is a widely prescribed diuretic and it is indicated for the treatment of edema, control of essential hypertension and management of diabetes insipidus. In the current article a new, accurate, sensitive, precise, rapid, reversed phase high performance liquid chromatography (RP-HPLC method was developed for determination of related substances of Telmisartan and Hydrochlorthiazide in tablet dosage form. Materials and Methods : Simultaneous determination of related substances was performed on Kromasil C 18 analytical column (250 × 4.6 mm; 5΅m pertical size column at 40°C employing a gradient elution. Mobile phase consisting of solvent A (solution containing 2.0 g of potassium dihydrogen phosphate anhydrous and 1.04 g of Sodium 1- Hexane sulphonic acid monohydrate per liter of water, adjusted to pH 3.0 with orthophosphoric acid and solvent B (mixture of Acetonitrile: Methanol in the ratio 80:20 v/v was used at a flow rate of 1.0 ml min−1 . UV detection was performed at 270 nm. Results : During method validation parameter such as precision, linearity, accuracy, specificity, limit of detection and quantification were evaluated, which remained within acceptable limits. Conclusions : HPLC analytical method is linear, accurate, precise, robust and specific, being able to separate the main drug from its degradation products. It may find application for the routine analysis of the related substances of both Telmisartan and Hydrochlorthiazide in this combination tablets.
Simultaneous Estimation of Ambroxol Hydrochloride and Cetirizine Hydrochloride in Pharmaceutical Tablet Dosage Form by Simultaneous Equation Spectrophotometric Method: A Quality Control Tool for Dissolution Studies
Deepak Sharma; Mankaran Singh; Dinesh Kumar; Gurmeet Singh
Ambroxol Hydrochloride and Cetirizine Hydrochloride are used for the treatment of bronchitis, cough, and allergy. A simple, economical, accurate, and precise method for simultaneous estimation of Ambroxol Hydrochloride and Cetirizine Hydrochloride in tablet dosage form has been developed. Simultaneous equation method based on measurement of absorbance at two wavelengths, that is, 244 nm and 230 nm, λmax of Ambroxol Hydrochloride and Cetirizine Hydrochloride in pH 6.8 phosphate buffer. Both of...
Uhumwangho, Michael U; Okor, Roland S
The dissolution characteristics of melt granulations of paracetamol in capsule and tablet dosage form were compared to determine whether the dissolution characteristics of the granules can be actualized by formulating them as rapidly disintegrating tablets. The term melt granulation refers here to the wax-matrix granules that were formed by triturating the drug powder (paracetamol) with a melted carnauba wax. The matrix granules were admixed with diluents (lactose, alpha-cellulose or microcrystalline cellulose) also in granular form to prevent size separation during encapsulation or tableting. The granules were filled into hard gelatin capsules (mean content weight, 500 +/- 6.2 mg) or tableted (mean weight 500 +/- 5.1 mg, and tensile strength 1.36 +/- 0.2 to 1.7 +/- 0.3 MN/m2). The capsules and tablets were subjected to disintegration and in vitro dissolution tests. The dissolution data were analyzed on the basis of zero, first order rate kinetics and Higuchi square root of time relationship. The results showed that the dissolution profiles were generally consistent with a first order rate kinetics (r = 0.95). The first order dissolution rate constants of capsules and tablets of the matrix granules only (without diluents) were 0.31 +/- 0.02 min(-1) and 0.20 +/- 0.03 min(-1), respectively, indicating faster dissolution from the capsules. Therefore, the dissolution characteristics of the matrix particles were not intact after tableting. Addition of diluents to the capsule formulations had no effect on dissolution rates, whereas in the tablets, dissolution rates increased. For instance, inclusion of a diluent up to 50% w/w in the tablets increased the dissolution rate constants to 0.34 +/- 0.04 min(-1) (lactose), 0.42 +/- 0.02 min(-1) (alpha-cellulose), and 0.46 +/- 0.03 min(-1) (microcrystalline cellulose). Thus, alpha-cellulose and microcrystalline cellulose produced greater enhancer effect on the tablet dissolution rates compared to lactose. Both the capsules and
Galløe, A.M.; Skagen, K.; Christensen, Niels Juel
The present study attempts to assess the efficacy combination therapy for heart failure. Genuine dose-response studies on combination therapy are not available and published studies involved adding one drug on top of 'usual treatment'. Sixteen different dosage combinations of trandolapril...... with the maximal effect at 0.5 mg daily. Both drugs significantly increased renin concentration with a significant potentiating interaction. It was not possible to detect beneficial effects of combination therapies. The optimal dosage of Bumetanide appeared to be 0.5 mg twice daily based on its effect on quality...... of life and weight loss. Estimated by the reduction in systolic blood pressure the optimal dosage of Trandolapril appeared to be 0.5 mg once daily. CONCLUSIONS: It appears that patients should be given less than the usually recommended dosages. Patients may be treated with a low dose loop diuretic...
Singh R; Saini P; Mathur S; Singh G; Lal B
The present work describes a simple, precise and accurate HPLC method for estimation of montelukast sodium in bulk and in tablet dosage form. The separation was achieved by using octadecylsilane column (C18) and acetonitrile:1 mM sodium acetate adjusted to pH 6.3 with acetic acid in proportion of 90:10 v/v as mobile phase, at a flow rate of 1.5 ml/min. Detection was carried out at 285 nm. The retention time of montelukast sodium was found to be 3.4 min. The limit of detection was found 1.31 &...
Qi, Xiaole; Chen, Haiyan; Rui, Yao; Yang, Fengjiao; Ma, Ning; Wu, Zhenghong
To prolong the residence time of dosage forms within gastrointestinal trace until all drug released at desired rate was one of the real challenges for oral controlled-release drug delivery system. Herein, we developed a fine floating tablet via compression coating of hydrophilic polymer (hydroxypropyl cellulose) combined with effervescent agent (sodium bicarbonate) to achieve simultaneous control of release rate and location of ofloxacin. Sodium alginate was also added in the coating layer to regulate the drug release rate. The effects of the weight ratio of drug and the viscosity of HPC on the release profile were investigated. The optimized formulations were found to immediately float within 30s and remain lastingly buoyant over a period of 12 h in simulated gastric fluid (SGF, pH 1.2) without pepsin, indicating a satisfactory floating and zero-order drug release profile. In addition, the oral bioavailability experiment in New Zealand rabbits showed that, the relative bioavailability of the ofloxacin after administrated of floating tablets was 172.19%, compared to marketed common release tablets TaiLiBiTuo(®). These results demonstrated that those controlled-released floating tables would be a promising gastro-retentive delivery system for drugs acting in stomach. Copyright © 2015 Elsevier B.V. All rights reserved.
Mallikarjuna Rao, Nagasarapu; Gowrisankar, Dannana
Pristinamycin is an antibiotic used mainly in the treatment of Staphylococcus infections. The aim of this study was to develop a rapid and simple stability-indicating RP-HPLC method for the determination of pristinamycin in tablet dosage form. Pristinamycin was eluted on the ACE-5, C18-HL, 250 x 4.6 mm, 5 µm analytical column with a mobile phase consisting of 0.2% orthophosphoric acid and acetonitrile 63:37 v/v, pumped at 1.5 ml/min flow rate. The column was maintained at 40°C and 10 μl of the solutions were injected. UV detection was performed at 206 nm. The procedure separated pristinamycin and its potential degradation products in an overall analysis time of less than 10 min with pristinamycin eluting at about 3 min. The method was validated according to the regulatory guidelines with respect to specificity, precision, accuracy, linearity, and robustness. Forced degradation studies were also performed for pristinamycin bulk drug samples to demonstrate the stability-indicating power of the HPLC method. The % RSD of system precision and method precision was found to be 0.64 and 1.49%, respectively. The procedure provided a linear response over the concentration range 25-150 μg/ml (r = 0.9998). Finally, the applicability of the method was evaluated in the tablet dosage form as well as in stability samples.
Singh, R M; Saini, P K; Mathur, S C; Singh, G N; Lal, B
The present work describes a simple, precise and accurate HPLC method for estimation of montelukast sodium in bulk and in tablet dosage form. The separation was achieved by using octadecylsilane column (C18) and acetonitrile:1 mM sodium acetate adjusted to pH 6.3 with acetic acid in proportion of 90:10 v/v as mobile phase, at a flow rate of 1.5 ml/min. Detection was carried out at 285 nm. The retention time of montelukast sodium was found to be 3.4 min. The limit of detection was found 1.31 µg/ml and limit of quantification 3.97 µg/ml. The accuracy and reliability of the proposed method was ascertained by evaluating various validation parameters like linearity (1-100 µg/ml), precision, accuracy and specificity according to ICH guidelines. The proposed method provides an accurate and precise quality control tool for routine analysis of montelukast sodium in bulk and in tablet dosage form.
Bioequivalence, Food Effect, and Steady-State Assessment of Dapagliflozin/Metformin Extended-release Fixed-dose Combination Tablets Relative to Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Subjects.
Chang, Ming; Liu, Xiaoni; Cui, Dapeng; Liang, Dan; LaCreta, Frank; Griffen, Steven C; Lubin, Susan; Quamina-Edghill, Donette; Boulton, David W
Simplification of therapeutic regimens for patients with type 2 diabetes mellitus can provide convenience that leads to improved compliance. Dapagliflozin/metformin extended-release (XR) fixed-dose combination (FDC) tablets offer the convenience of once-daily dosing. Two pharmacokinetic (PK) studies were conducted to establish bioequivalence for 2 doses of dapagliflozin/metformin XR FDC versus the same dosage of the individual component (IC) tablets in healthy adults. Two open-label, randomized, 4-period, 4-arm crossover studies were conducted to assess the bioequivalence and PK properties of dapagliflozin and metformin FDCs in healthy subjects under fed and fasting conditions. Participants received single oral doses or once-daily dosing of dapagliflozin/metformin XR (5 mg/500 mg [study 1] or 10 mg/1000 mg [study 2]) for 4 days in an FDC formulation or corresponding strengths of IC tablets. For both of the studies, dapagliflozin and metformin 5 mg/500 mg or 10 mg/1000 mg FDC tablets were bioequivalent to the respective IC tablets. The 90% CIs of the ratio of the adjusted geometric means for all key PK parameters (Cmax, AUC0-T, and AUC0-∞) were contained within the predefined 0.80 to 1.25 range to conclude bioequivalence for both dapagliflozin and metformin. Once-daily dosing to steady state of each FDC tablet had no effect on the PK properties of dapagliflozin or metformin. When the FDCs were administered with a light-fat meal, there was no effect on metformin PK values and only a modest, nonclinically meaningful effect on dapagliflozin PK values. There were no safety or tolerability concerns. Bioequivalence of the FDCs of dapagliflozin/metformin XR and the ICs was established, and no safety issues of clinical concern were raised. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.
Wang, Yongjun; Liu, Hongzhuo; Liu, Kai; Sun, Jin; He, Zhonggui
In order to improve the bioavailability of rifampicin (RIF) from rifampicin and isoniazid (INH) combination formulations, the physicochemical characteristics of RIF, stability of RIF in different pH buffers in the presence of INH, as well as the effect of particle size of RIF materials on the dissolution rate were investigated. On the basis of the above examinations, enteric-coated tablets for RIF and INH combinations were designed and prepared. RIF showed low solubility and high apparent distribution coefficient in the intestinal pH (pH 4.0-7.4). With the decrease in pH, the degradation of RIF increase and the presence of INH deepen the degradation. Enteric-coated tablets were prepared after grinding the RIF materials by dry granulation technique. The pharmacokinetics of RIF and INH of self-made enteric-coated tablets in dogs were studied by comparing with the reference tablets. The AUC(0-48) of RIF in both reference and test tablets were 304.77 ± 42.27 and 353.79 ± 31.63 µg·h·mL(-1), respectively. The AUC(0-48) of INH in both reference and test tablets were 17.14 ± 8.59 and 19.62 ± 10.57 µg·h·mL(-1), respectively. Enteric-coated tablets may minimize the decomposition of RIF in gastrointestinal tract and improve the bioavailability.
Huang, Yaw-Bin; Tsai, Yi-Hung; Yang, Wan-Chiech; Chang, Jui-Sheng; Wu, Pao-Chu; Takayama, Kozo
The purpose of this study was to develop and optimize the propranolol once-daily extended release formulations containing HPMC, Microcrystalline cellulose (MCC) and lactose. In vitro studies, the response surface methodology and multiple response optimization utilizing the polynomial equation were used to search for the optimal formulation with specific release rate at different time intervals. The constrained mixture experimental design was used to prepare systematic model formulations, which were composed of three formulation variables: the content of HPMC (X(1)) MCC (X(2)) and lactose (X(3)). The drug release percent at 1.5, 4, 8, 14 and 24 h were the target responses and were restricted to 15-30, 35-55, 55-75, 75-90 and 90-110%, respectively. The results showed that the optimized formulation provided a dissolution pattern equivalent to the predicted curve, which indicated that the optimal formulation could be obtained using response surface methodology. The mechanism of drug release from HMPC matrix tablets followed non-Fickian diffusion. In the vivo study, the MRT was prolonged for matrix tablets when compared with commercial immediate release tablets. Furthermore, a linear relationship between in vitro dissolution and in vivo absorption was observed in the beagle dogs.
Rahim, Najia; Naqvi, Syed Baqir-Shyum; Bibi, Rehana; Iffat, Wajiha; Shakeel, Sadia; Muhammad, Iyad Naeem
Fast Disintegrating Tablets (FDTs) is a rapidly growing dosage form preferred for special population (pediatric, geriatric and psychotic patients). It is also developed with the aim of improving bioavailability and patient compliance. During the present study, cefadroxil fast disintegrating tablets formulations (n=9) were designed and optimized by central composite design with two independent variables (croscarmellose and crospovidone) using design expert® software. The effects of independent variables on formulation properties such as friability, hardness, in vitro dispersion and disintegration were assessed by drawing response surface graphs with design expert® software. Tablets were assessed for pharmacopeial and non-pharmacopeial parameters to ensure the quality of compressed tablets. Among all formulations, F3, F8 and F9 have shown better results. The formulation F9 containing 15mg croscarmellose and 33.075mg crospovidone showed good pharmacotechnical attributes as well as shelf life. F 9 showed improved dissolution with t90% of> 2 min and will lead to better bioavailability.
Ozkan, Y; Yilmaz, N; Ozkan, S A; Biryol, I
A high-performance liquid chromatographic procedure with two detectors is presented for the determination of verapamil in pharmaceutical dosage forms. The procedure is based on the use of reversed-phase high-performance liquid chromatography with UV and fluorimetric detectors. Each analysis required no longer than 6 min for both detection procedures. Quantification was achieved by measurement of the ratio of the peak area of the drug to the internal standard (fluoxetine) and the detection limit was 10 ng/ml for the UV detector and 750 pg/ml for the fluorimetric detector. There was no significant difference between inter- and intra-day studies for verapamil determined for two different concentrations (0.05 and 1.00 microgram/ml). This process could be used to determine verapamil concentrations in the range 0.025-50 and 0.0008-20 micrograms/ml for UV and fluorimetric detection, respectively. These methods were applied, without any interference from the excipients, for the determination of the drug in tablets and in drug dissolution studies. It is suggested that the proposed HPLC procedures could be used for routine quality control and dosage form assay of verapamil hydrochloride.
Full Text Available Two simple and sensitive spectrophotometric methods have been developed for the determination of simvastatin (SMT in pure form and in tablets using insitu generated bromine, and p-phenylenediamine (PPDA or o-dianisidine (ODA as reagents. The methods are based on the bromination of SMT by a measured excess of in situ bromine in acid medium followed by the determination of unreacted bromine by reacting with PPDA and measuring the resulting red colour at 510 nm (method A or reacting with ODA and measuring the absorbance at 470 nm (method B. The conditions for the assay have been optimized. Beer’s law is obeyed over the concentration ranges 20-120 and 2- -12 μg/ml for method A and method B, respectively. The calculated molar absorbtivities are 2.24×103 and 1.91×104 dm3 mol-1 cm-1 for the method A and the method B, respectively; 0.1868 and 0.0115 μg/cm2 being the corresponding Sandell sensitivities. The LOD and LOQ for method A are found to be 2.96 and 8.97 μg/ml, and the respective values for method B are 0.14 and 0.42 μg/ml. The intra-day and inter-day precision and accuracies were checked. The assay precision was less than 5 % CV and the accuracy was 97.38-103.4 %. The methods were used for the determination of SMT in tablets. No interference from the excipients added to tablets was found. The accuracy and validity of the methods were further ascertained by recovery studies via the standard addition technique.
D. Hamish Wright, PhD
Conclusions: The combination tablet was considered bioequivalent to coadministration based on ALN AUC0–∞ and unadjusted vitamin D3 parameters. Slight differences for ALN AUC0–last and Cmax (upper 90% CIs outside the bounds were not considered clinically significant. The combination tablet was well tolerated. No serious adverse experiences were reported. © 2015. The Authors. Published by Elsevier Inc. All rights reserved.
Jongbloed-de Hoon, M.; Colbers, A.; Velthoven-Graafland, K.; Duisenberg-van Essenberg, M.; Kruijssen, M.; Abbink, E.; Crevel, R. van; Burger, D.M.
We investigated whether a fixed-dose combination tablet of elvitegravir, cobicistat, emtricitabine, and tenofovirDF (Stribild) can be crushed and combined with enteral nutrition without influencing pharmacokinetics. This was an open-label, 3-period, single-dose, randomized, crossover trial in 24
Attia, Tamer Z.
A simple, rapid, sensitive and selective high performance liquid chromatographic (HPLC) method with ultraviolet detection has been developed for simultaneous determination of ascorbic acid and rutin in pure forms and pharmaceutical dosage form. HPLC separation was performed on Phenomenex C18 analytical column with 0.1% v/v acetic acid in water and acetonitrile (75:25, v/v), as mobile phase. The separation was done at ambient temperature with flow rate of 1 mL·min- 1 in isocratic mode. HPLC measurements were carried out using ultraviolet detection wavelength at 257 nm. The average retention times were 2.72 and 7.00 min for ascorbic acid and rutin, respectively. The calibration plots were constructed over the concentration range of 5.0-30.0 for ascorbic acid and 10.0-60.0 μg·mL- 1 for rutin. The limits of detection were 1.06 and 1.89 μg·mL- 1 and limits of quantification were 3.54 and 6.31 μg·mL- 1 for ascorbic acid and rutin, respectively. The proposed HPLC-UV method was successfully applied for determination of ascorbic acid in its tablets and for simultaneous determination of the studied drugs in their laboratory prepared mixtures and in pharmaceutical formulation. Statistical comparisons of the results with the reference method show an excellent agreement and indicate no significant difference in respect to accuracy and precision.
Palo, Mirja; Kogermann, Karin; Laidmäe, Ivo; Meos, Andres; Preis, Maren; Heinämäki, Jyrki; Sandler, Niklas
Printing technology has been shown to enable flexible fabrication of solid dosage forms for personalized drug therapy. Several methods can be applied for tailoring the properties of the printed pharmaceuticals. In this study, the use of electrospun fibrous substrates in the fabrication of inkjet-printed dosage forms was investigated. A single-drug formulation with lidocaine hydrochloride (LH) and a combination drug system containing LH and piroxicam (PRX) for oromucosal administration were prepared. The LH was deposited on the electrospun and cross-linked gelatin substrates by inkjet printing, whereas PRX was incorporated within the substrate fibers during electrospinning. The solid state analysis of the electrospun substrates showed that PRX was in an amorphous state within the fibers. Furthermore, the results indicated the entrapment and solidification of the dissolved LH within the fibrous gelatin matrix. The printed drug amount (2-3 mg) was in good correlation with the theoretical dose calculated based on the printing parameters. However, a noticeable degradation of the printed LH was detected after a few months. An immediate release (over 85% drug release after 8 min) of both drugs from the printed dosage forms was observed. In conclusion, the prepared electrospun gelatin scaffolds were shown to be suitable substrates for inkjet printing of oromucosal formulations. The combination of electrospinning and inkjet printing allowed the preparation of a dual drug system.
Tanner, Trevor; Aspley, Sue; Munn, Andrew; Thomas, Tracy
Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-over, repeat-dose study. Pharmacokinetic parameters for ibuprofen and paracetamol were similar for the combination and monotherapy tablets (values falling within the 80% to 125% acceptable bioequivalence range) except for the rate of absorption of paracetamol from the combination (tmax), which was significantly faster compared with monotherapy (median difference 10 minutes; p ibuprofen from the combination, compared with 0.58 microg x mL(-1) and 9.00 microg x mL-1, respectively, for monotherapy. For paracetamol, mean plasma levels at 10 and 20 minutes were 5.43 microg x mL(-1) and 14.54 microg x mL(-, respectively, for the combination compared with 0.33 microg x mL(-1) and 9.19 microg x mL(-1), respectively, for monotherapy. The rate of absorption of both ibuprofen and paracetamol was significantly delayed when the combination tablet was administered in the fed versus fasted state; median delay was 25 minutes for ibuprofen (p > 0.05) and 55 minutes for paracetamol (p ibuprofen and paracetamol in a fixed-dose combination tablet does not significantly alter the pharmacokinetic profiles of either drug, except for enhancing the rate of paracetamol absorption, offering potential therapeutic benefits in relation to the onset of analgesia. Concentrations of both drugs reached previously reported therapeutic levels when the combination tablet was administrated in the fed or fasted state. Three times daily dosing may offer enhanced therapeutic effect for longer than twice daily dosing.
Liu, S. F.
A sensitive method based on the fluorescence enhancement was developed for the determination of rutin. It was found that the rutin could form a fluorescent complex with ytterium (III), and the fluorescence intensity of which could be enhanced by sodium dodecyl benzene sulfonate. Under the optimum conditions, the enhanced fluorescence intensity was in proportion to the concentration of rutin in the range of 12-1200 ng/ml and the detection limit (S/N=3) was 1.3 ng/ml. This method possessed the properties of simplicity, fast assay process and high sensitivity, and has been satisfactorily applied for the analysis of actual sample. The possible interaction mechanism of this system was also discussed in this manuscript. PMID:24403666
Bredenberg, Susanne; Nyholm, Dag; Aquilonius, Sten Magnus; Nyström, Christer
A new concept for individualising the dosage of drugs in solid form is presented. The principle is based on the use of standardised units (microtablets), each containing a subtherapeutic amount of the active ingredient. The required dose is fine-tuned by counting out a specific number of these units. The microtablets are counted electronically from the attached cassette by the automatic dispensing device. The individual dose is set and the dispenser counts and delivers the correct number of microtablets. The usefulness of the automatic dispenser concept and acceptability of the apparatus were evaluated in patients with Parkinson's disease (PD). After initial instruction on use of the dispenser, 20 patients operated it themselves. All patients were generally satisfied with their management of the automatic dispenser and most would be happy to use the device again. Further technical development is required before use in clinical practice, but the current prototype may be acceptable for some patients. It is concluded that the final version of the automatic dose dispenser concept will offer potential for improvement of drug administration for patients with PD or other diseases requiring individual dosage.
H. Liedgens (Hiltrud); M.J.C. Nuijten (Mark); B.P. Nautrup (Barbara Poulsen)
textabstractObjective: To compare the costs of treating osteoarthritis (OA) pain using combination tramadol/paracetamol tablets, NSAIDs alone, NSAIDs plus proton pump inhibitors (PPIs), or NSAIDs plus histamine H2-receptor antagonists (H2RAs) from the perspective of the Dutch healthcare system.
Application of smart spectrophotometric methods and artificial neural network for the simultaneous quantitation of olmesartan medoxamil, amlodipine besylate and hydrochlorothiazide in their combined pharmaceutical dosage form
Background New, simple and specific spectrophotometric methods and artificial neural network (ANN) were developed and validated in accordance with ICH guidelines for the simultaneous estimation of Olmesartan (OLM), Amlodipine (AML), and Hydrochlorothiazide (HCT) in commercial tablets. Results For spectrophotometric methods: First, Amlodipine (AML) was determined by direct spectrophotometry at 359 nm and by application of the ratio subtraction, the AML spectrum was removed from the mixture spectra. Then Hydrochlorothiazide (HCT) was determined directly at 315 nm without interference from Olmesartan medoxamil (OLM) which could be determined using the isoabsorptive method. The calibration curve is linear over the concentration range of 5–40, 2.5-40 and 2–40 μg mL-1 for AML, OLM and HCT, respectively. ANN (as a multivariate calibration method) was also applied for the simultaneous determination of the three analytes in their combined pharmaceutical dosage form using spectral region from 230–340 nm. Conclusions The proposed methods were successfully applied for the assay of the three analytes in laboratory prepared mixtures and combined pharmaceutical tablets with excellent recoveries. No interference was observed from common pharmaceutical additives. The results were favorably compared with those obtained by a reference spectrophotometric method. The methods are validated according to the ICH guidelines and accuracy, precision and repeatability are found to be within the acceptable limit. PMID:23374392
Gabbott, Ian P; Al Husban, Farhan; Reynolds, Gavin K
A pharmaceutical compound was used to study the effect of batch wet granulation process parameters in combination with the residual moisture content remaining after drying on granule and tablet quality attributes. The effect of three batch wet granulation process parameters was evaluated using a multivariate experimental design, with a novel constrained design space. Batches were characterised for moisture content, granule density, crushing strength, porosity, disintegration time and dissolution. Mechanisms of the effect of the process parameters on the granule and tablet quality attributes are proposed. Water quantity added during granulation showed a significant effect on granule density and tablet dissolution rate. Mixing time showed a significant effect on tablet crushing strength, and mixing speed showed a significant effect on the distribution of tablet crushing strengths obtained. The residual moisture content remaining after granule drying showed a significant effect on tablet crushing strength. The effect of moisture on tablet tensile strength has been reported before, but not in combination with granulation parameters and granule properties, and the impact on tablet dissolution was not assessed. Correlations between the energy input during granulation, the density of granules produced, and the quality attributes of the final tablets were also identified. Understanding the impact of the granulation and drying process parameters on granule and tablet properties provides a basis for process optimisation and scaling. Copyright © 2016 Elsevier B.V. All rights reserved.
Wu, Lan; Leng, Donglei; Cun, Dongmei
Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy...... using different pharmaceuticals has been proven highly effective due to the ability to affect multiple cellular pathways involved in the disease progression. However, the currently used drug combination designs are primarily based on empirical clinical studies, and little attention has been given...... for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials....
Abebe, Admassu; Akseli, Ilgaz; Sprockel, Omar; Kottala, Niranjan; Cuitiño, Alberto M
Therapeutic strategies based on oral delivery of bilayer (and multilayer) tablets are gaining more acceptance among brand and generic products due to a confluence of factors including advanced delivery strategies, patient compliance and combination therapy. Successful manufacturing of these ever more complex systems needs to overcome a series of challenges from formulation design to tablet press monitoring and control. This article provides an overview of the state-of-the-art of bilayer tablet technology, highlighting the main benefits of this type of oral dosage forms while providing a description of current challenges and advances toward improving manufacturing practices and product quality. Several aspects relevant to bilayer tablet manufacturing are addressed including material properties, lubrication, layer ordering, layer thickness, layer weight control, as well as first and final compression forces. A section is also devoted to bilayer tablet characterization that present additional complexities associated with interfaces between layers. The available features of the manufacturing equipment for bilayer tablet production are also described indicating the different strategies for sensing and controls offered by bilayer tablet press manufacturers. Finally, a roadmap for bilayer tablet manufacturing is advanced as a guideline to formulation design and selection of process parameters and equipment. Copyright © 2013 Elsevier B.V. All rights reserved.
Miao, Rong-ming; Sun, Xian-feng; Zhang, Ying-yi; Wu, Wei; Fang, Zhong-hua; Zhao, Rui; Zhao, Dao-kun; Qian, Gui-liang; Ji, Jie
To observe the clinical efficacy of tetrandrine combined with acetylcysteine effervescent tablets in the treatment of silicosis. A total of 96 patients with silicosis were randomly divided into treatment group (49 cases) and control group (47 cases). Both groups were given routine therapy including anti-inflammatory, antitussive, and antiasthmatic drugs, and the patients in treatment group were given tetrandrine combined with acetylcysteine effervescent tablets at the same time. Tetrandrine (100 mg) was orally administrated twice a day, and there was a one-day interval between every 6 days' continuous administration; totally, there were four courses of treatment, with 3 months for each course, and there was a one-month break between each course. Acetylcysteine effervescent tablets (600 mg) were taken twice a day; each course of treatment was 12 days, and there were four courses; for the first two months, there was one course per month, and then one course every other two months for the rest of time. Clinical symptoms, pulmonary ventilation function, serum superoxide dismutase (SOD) and changes in X-ray findings were observed. After treatment, the treatment group had significantly increased rates of improvements in cough, expectoration, chest congestion and pain, and dyspnea compared with the control group (P silicosis. The combination of tetrandrine and acetylcysteine effervescent tablets show some effect in the treatment of silicosis. It can be an effective option for treating silicosis as there are no other specific remedies.
Hemavathi N. Deepakumari
Full Text Available Three simple, accurate and highly sensitive indirect spectrophotometric methods have been developed for the determination of oxcarbazepine (OXC in both pure and in pharmaceutical preparations. The methods are based on the oxidation of oxcarbazepine by a known excess of cerium(IV in acid medium. This was followed by the determination of unreacted cerium(IV, which oxidizes leuco dyes to colored dyes in the same acid medium. In method A, an unreacted cerium(IV oxidizes leuco crystal violet to crystal violet dye which is measured at 580 nm. A bluish-colored malachite green with a maximum absorption at 610 nm is developed in method B. In method C, cerium(IV oxidizes leuco xylene cyanol FF to blue colored xylene cyanol FF having absorption maximum at 610 nm. In all these methods, the amount of cerium(IV reacted corresponds to the amount of OXC and the absorbance is found to decrease linearly with OXC concentration. Beer’s law was obeyed in the concentration range of 0–2.5, 0–2.0 and 0–2.5 μg ml−1 for methods A, B and C, respectively, and the corresponding molar absorptivity values are 3.86 × 104, 4.41 × 104 and 2.16 × 104 l mol−1cm−1. All variables have been optimized and the results were statistically compared with those of a literature method by employing the student’s t-test and F-test. No interference was observed from excipients normally added to the tablets.
Background Levofloxacin hemihydrate (LEV) and ambroxol HCl (AMB) are available for the treatment of upper and lower respiratory tract infections. A survey of the literature reveals that two reversed phase HPLC methods were e reported for the simultaneous determination of LEV and AMB in pharmaceutical preparations. However the reported methods suffers from the low sensitivity, no application of the method in the combined tablets and no application to biological fluids. Also the toxic effects of the used solvents which are harmful to human beings. For this reason, our target was to develop a simple sensitive, less hazardous micellar HPLC method for the simultaneous determination of LEV and AMB in their combined dosage forms and plasma. Results The method showed good linearity over the ranges of 1–44 μg/mL and 1–20 μg/mL with limits of detection 0.26 and 0.07 μg/mL and limits of quantification 0.80 and 0.20 μg/mL for LEV and AMB, respectively. The method was further extended to the determination of LEV in spiked human plasma with mean percentage recoveries of 100.10% ± 1.14 as well as determination of LEV in real human plasma without prior extraction. Statistical evaluation of the data was performed according to ICH Guidelines. Conclusion The suggested method was successfully applied for the simultaneous analysis of the studied drugs in their co-formulated tablets and human plasma. The mean percentage recoveries in combined tablets were 100.20 ± 1.64 and 100.72 ± 1.11 for LEV and AMB, respectively and 100.10 ± 1.14 for LEV in spiked human plasma. Statistical comparison of the results with those of the comparison method revealed good agreement and proved that there were no significant difference in the accuracy and precision between the two methods respectively. PMID:24079576
Pathak, A; Rajput, S J
Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations...
El-Enany Nahed M
Full Text Available Abstract Background Rosiglitazone (ROZ and glimepiride (GLM are antidiabetic agents used in the treatment of type 2 diabetes mellitus. A survey of the literature reveals that only one spectrophotometric method has been reported for the simultaneous determination of ROS and GLM in pharmaceutical preparations. However the reported method suffers from the low sensitivity, for this reason, our target was to develop a simple sensitive HPLC method for the simultaneous determination of ROZ and GLM in their combined dosage forms and plasma. Results A simple reversed phase high performance liquid chromatographic (RP-HPLC method was developed and validated for the simultaneous determination of Rosiglitazone (ROS and Glimepiride (GLM in combined dosage forms and human plasma. The separation was achieved using a 150 mm × 4.6 mm i.d., 5 μm particle size Symmetry® C18 column. Mobile phase containing a mixture of acetonitrile and 0.02 M phosphate buffer of pH 5 (60: 40, V/V was pumped at a flow rate of 1 mL/min. UV detection was performed at 235 nm using nicardipine as an internal standard. The method was validated for accuracy, precision, specificity, linearity, and sensitivity. The developed and validated method was successfully used for quantitative analysis of Avandaryl™ tablets. The chromatographic analysis time was approximately 7 min per sample with complete resolution of ROS (tR = 3.7 min., GLM (tR = 4.66 min., and nicardipine (tR, 6.37 min. Validation studieswas performed according to ICH Guidelines revealed that the proposed method is specific, rapid, reliable and reproducible. The calibration plots were linear over the concentration ranges 0.10-25 μg/mL and 0.125-12.5 μg/mL with LOD of 0.04 μg/mL for both compounds and limits of quantification 0.13 and 0.11 μg/mL for ROS and GLM respectively. Conclusion The suggested method was successfully applied for the simultaneous analysis of the studied drugs in their co-formulated tablets and human
McCormick, T J; Gibson, A B; Diana, F J
A dissolution method for warfarin sodium-aspirin combination tablets was developed which utilizes USP Apparatus 1 (baskets) at 50 rpm with 900 ml of phosphate buffer (pH 6.8; 0.05 M) medium at 37 degrees C. A reversed-phase liquid chromatographic method was also developed for the simultaneous determination of warfarin sodium, aspirin and salicylic acid on an octadecylsilica column using acetonitrile-tetrahydrofuran-glacial acetic acid-water (23:5:5:67, v/v/v/v) as the mobile phase with UV detection at 282 nm. Validation data were obtained which demonstrate that the dissolution methodology is accurate, precise, linear and rugged for the combination tablets.
Shaikh, K A; Patil, S D; Devkhile, A B
A simple, precise and accurate reversed-phase liquid chromatographic method has been developed for the simultaneous estimation of ambroxol hydrochloride and azithromycin in tablet formulations. The chromatographic separation was achieved on a Xterra RP18 (250 mm x 4.6 mm, 5 microm) analytical column. A Mixture of acetonitrile-dipotassium phosphate (30 mM) (50:50, v/v) (pH 9.0) was used as the mobile phase, at a flow rate of 1.7 ml/min and detector wavelength at 215 nm. The retention time of ambroxol and azithromycin was found to be 5.0 and 11.5 min, respectively. The validation of the proposed method was carried out for specificity, linearity, accuracy, precision, limit of detection, limit of quantitation and robustness. The linear dynamic ranges were from 30-180 to 250-1500 microg/ml for ambroxol hydrochloride and azithromycin, respectively. The percentage recovery obtained for ambroxol hydrochloride and azithromycin were 99.40 and 99.90%, respectively. Limit of detection and quantification for azithromycin were 0.8 and 2.3 microg/ml, for ambroxol hydrochloride 0.004 and 0.01 microg/ml, respectively. The developed method can be used for routine quality control analysis of titled drugs in combination in tablet formulation.
Bienczak, A.; Denti, P.; Cook, A.; Wiesner, L.; Mulenga, V.; Kityo, C.; Kekitiinwa, A.; Gibb, D.M.; Burger, D.M.; Walker, A.S.; McIlleron, H.
BACKGROUND: Nevirapine is the only nonnucleoside reverse transcriptase inhibitor currently available as a paediatric fixed-dose-combination tablet and is widely used in African children. Nonetheless, the number of investigations into pharmacokinetic determinants of virological suppression in African
Rasha A. Shaalan
Full Text Available Simple and selective HPTLC methods were developed for the simultaneous determination of the antihypertensive drugs; carvedilol and hydrochlorothiazide in their binary mixture (Mixture I and amlodipine besylate, valsartan, and hydrochlorothiazide in their combined ternary formulation (Mixture II. Effective chromatographic separation was achieved on Fluka TLC plates 20 × 20 cm aluminum cards, 0.2 mm thickness through linear ascending development. For Mixture I, the mobile phase composed of chloroform–methanol in the ratio 8:2 v/v. Detection was performed at 254 nm for both carvedilol and hydrochlorothiazide. For Mixture II, the mobile phase was chloroform–methanol–ammonia in the volume ratio 8:2:0.1. Detection was performed at 254 nm for valsartan and hydrochlorothiazide, and at 365 nm for amlodipine. Quantification was based on spectrodensitometric analysis. Analytical performance of the proposed HPTLC procedures was statistically validated with respect to linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. The linearity ranges were 0.05–1.0 and 0.1–2.0 μg/spot for carvedilol and hydrochlorothiazide, respectively in Mixture I, 0.1–2.0, 0.1–2.0 and 0.2–4.0 μg/spot for amlodipine, hydrochlorothiazide and valsartan, respectively in Mixture II, with correlation coefficients >0.9992. The validated HPTLC methods were applied to the analysis of the cited antihypertensive drugs in their combined pharmaceutical tablets. The proposed methods confirmed peak identity and purity.
Salazar, Jaime; Müller, Rainer H; Möschwitzer, Jan P
Standard particle size reduction techniques such as high pressure homogenization or wet bead milling are frequently used in the production of nanosuspensions. The need for micronized starting material and long process times are their evident disadvantages. Combinative particle size reduction technologies have been developed to overcome the drawbacks of the standard techniques. The H 42 combinative technology consists of a drug pre-treatment by means of spray-drying followed by standard high pressure homogenization. In the present paper, spray-drying process parameters influencing the diminution effectiveness, such as drug and surfactant concentration, were systematically analyzed. Subsequently, the untreated and pre-treated drug powders were homogenized for 20 cycles at 1500 bar. For untreated, micronized glibenclamide, the particle size analysis revealed a mean particle size of 772 nm and volume-based size distribution values of 2.686 μm (d50%) and 14.423 μm (d90%). The use of pre-treated material (10:1 glibenclamide/docusate sodium salt ratio spray-dried as ethanolic solution) resulted in a mean particle size of 236 nm and volume-based size distribution values of 0.131 μm (d50%) and 0.285 μm (d90%). These results were markedly improved compared to the standard process. The nanosuspensions were further transferred into tablet formulations. Wet granulation, freeze-drying and spray-drying were investigated as downstream methods to produce dry intermediates. Regarding the dissolution rate, the rank order of the downstream processes was as follows: Spray-drying>freeze-drying>wet granulation. The best drug release (90% within 10 min) was obtained for tablets produced with spray-dried nanosuspension containing 2% mannitol as matrix former. In comparison, the tablets processed with micronized glibenclamide showed a drug release of only 26% after 10 min. The H 42 combinative technology could be successfully applied in the production of small drug nanocrystals. A
Full Text Available The purpose of this study was to develop an extended-release (ER matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate (HPMCAS and hydroxypropylcellulose (HPC were selected as ER polymers for the ER matrix tablet (HPMCAS/HPC ER matrix tablet. Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed. In a USP apparatus 3 (bio-relevant dissolution method, dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product (OxyContin. Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroPlus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.
Vu Dang Hoang
Full Text Available The application of first-order derivative and wavelet transforms to UV spectra and ratio spectra was proposed for the simultaneous determination of ibuprofen and paracetamol in their combined tablets. A new hybrid approach on the combined use of first-order derivative and wavelet transforms to spectra was also discussed. In this application, DWT (sym6 and haar, CWT (mexh, and FWT were optimized to give the highest spectral recoveries. Calibration graphs in the linear concentration ranges of ibuprofen (12–32 mg/L and paracetamol (20–40 mg/L were obtained by measuring the amplitudes of the transformed signals. Our proposed spectrophotometric methods were statistically compared to HPLC in terms of precision and accuracy.
Hoang, Vu Dang; Ly, Dong Thi Ha; Tho, Nguyen Huu; Nguyen, Hue Minh Thi
The application of first-order derivative and wavelet transforms to UV spectra and ratio spectra was proposed for the simultaneous determination of ibuprofen and paracetamol in their combined tablets. A new hybrid approach on the combined use of first-order derivative and wavelet transforms to spectra was also discussed. In this application, DWT (sym6 and haar), CWT (mexh), and FWT were optimized to give the highest spectral recoveries. Calibration graphs in the linear concentration ranges of ibuprofen (12-32 mg/L) and paracetamol (20-40 mg/L) were obtained by measuring the amplitudes of the transformed signals. Our proposed spectrophotometric methods were statistically compared to HPLC in terms of precision and accuracy.
Hoang, Vu Dang; Ly, Dong Thi Ha; Tho, Nguyen Huu; Minh Thi Nguyen, Hue
The application of first-order derivative and wavelet transforms to UV spectra and ratio spectra was proposed for the simultaneous determination of ibuprofen and paracetamol in their combined tablets. A new hybrid approach on the combined use of first-order derivative and wavelet transforms to spectra was also discussed. In this application, DWT (sym6 and haar), CWT (mexh), and FWT were optimized to give the highest spectral recoveries. Calibration graphs in the linear concentration ranges of ibuprofen (12–32 mg/L) and paracetamol (20–40 mg/L) were obtained by measuring the amplitudes of the transformed signals. Our proposed spectrophotometric methods were statistically compared to HPLC in terms of precision and accuracy. PMID:24949492
A randomised, five-parallel-group, placebo-controlled trial comparing the efficacy and tolerability of analgesic combinations including a novel single-tablet combination of ibuprofen/paracetamol for postoperative dental pain.
Daniels, Stephen E; Goulder, Michael A; Aspley, Sue; Reader, Sandie
Combination analgesia is often recommended for the relief of severe pain. This was a double-blind, 5-arm, parallel-group, placebo-controlled, randomised, single-dose study designed to compare the efficacy and tolerability of a novel single-tablet combination of ibuprofen and paracetamol with that of an ibuprofen/codeine combination, and a paracetamol/codeine combination, using the dental impaction pain model. Subjects with at least 3 impacted third molars and experiencing moderate to severe postoperative pain were randomised to receive: 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg; 2 tablets of ibuprofen 200 mg/codeine 12.8mg; 2 tablets of paracetamol 500mg/codeine 15mg; or placebo. Results for the primary endpoint, the sum of the mean scores of pain relief combined with pain intensity differences over 12hours, demonstrated that 1 and 2 tablets of the single-tablet combination of ibuprofen/paracetamol were statistically significantly more efficacious than 2 tablets of placebo (Pparacetamol/codeine (P⩽0.0001); furthermore, 2 tablets offered significantly superior pain relief to ibuprofen/codeine (P=0.0001), and 1 tablet was found noninferior to this combination. Adverse events were uncommon during this study and treatment emergent adverse events were statistically significantly less frequent in the groups taking the ibuprofen/paracetamol combination compared with codeine combinations. In conclusion, 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg provided highly effective analgesia that was comparable with, or superior to, other combination analgesics currently indicated for strong pain. A single-tablet combination of ibuprofen 200mg/paracetamol 500mg provides highly effective analgesia, comparable or superior to other combination analgesics indicated for strong pain. Copyright © 2011. Published by Elsevier B.V.
Wolfe, Lisa L; Fisher, Mark C; Davis, Tracy R; Miller, Michael W
We compared dosages of a combination of sedatives, which included butorphanol tartrate, azaperone tartrate, and medetomidine HCl (BAM) in captive adult Rocky Mountain elk (Cervus elaphus nelsoni). All three BAM dosages (low, medium, and high) effectively immobilized elk and produced an adequate level of sedation in all subjects. Induction times were similar among the three groups (mean ± SD: low=6.9 ± 1.1 min; medium=6.3 ± 0.9 min; high=4.7 ± 1.3 min). Most elk became hypoxemic regardless of BAM dosage, but hypoxemia tended to be most severe in the high-BAM group; regardless of BAM dosage, oxygen supplementation improved the percentage of oxygen saturation and stabilized the vital rates. Recovery after administration of antagonists (3 mg atipamezole/mg medetomidine and 2 mg/kg tolazoline) was comparable among groups (range of means=9 ± 1.5-11.7 ± 1 min). Based on the findings from clinical trials and field data from free-ranging elk immobilizations, we recommend low-dose BAM (2 mL dose; equivalent to 46 mg butorphanol, 30 mg azaperone, and 18 mg medetomidine) and supplemental oxygen for adult elk; immobilization should be antagonized using 3-5 mg atipamezole/mg medetomidine and 2 mg/kg tolazoline, with tolazoline injected about 5-10 min before atipamezole to smooth out recovery.
Aleksovski, Aleksandar; Dreu, Rok; Gašperlin, Mirjana; Planinšek, Odon
Mini-tablets represent a new trend in solid dosage form design, with the main goal of overcoming some therapeutic obstacles such as impaired swallowing and polypharmacy therapy, and also offering some therapeutic benefits such as dose flexibility and combined release patterns. Mini-tablets are a promising patient-friendly drug delivery system. Mini-tablets are tablets with a diameter ≤ 3 mm produced on conventional tablet presses equipped with multiple tooling. Mini-tablet production is similar to the production of standard tablets but requires excellent powder flow due to the small dies, exact control of process parameters and special caution during tablet press assembly in order to avoid tool damage. Mini-tablets (coated or uncoated and single- or multiple-unit systems) are mainly developed as patient-friendly systems for pediatric and geriatric patients and also for personalized medicine because they offer improved swallowing and flexible dosing, combining various release kinetics, doses and active compounds in only one system. Mini-tablets may also be successfully used as multiple-unit modified release systems (extended release, delayed-colon release, pulsatile and bi-modal release and gastroretentive systems) providing improved drug bioavailability compared with single-unit systems. Mini-tablets used as single- or multiple-unit oral dosage forms have enormous potential as a patient-friendly drug delivery system for targeted populations, providing improved swallowing, flexible dosing and a combination of different release patterns and/or different active compounds (decreasing dosing frequency and/or polypharmacy therapy problems). In terms of complete expression of the benefits of mini-tablets over other oral dosage forms on the market, further investigation in formulation possibilities and development of suitable dosing devices is of essential importance.
He, Y-L; Paladini, S; Sabia, H; Campestrini, J; Zhang, Y; Leon, S; Ligueros-Saylan, M; Jarugula, V
To assess the bioequivalence of vildagliptin/metformin fixed-dose combination tablets (at doses of 50/500, 50/850 and 50/1,000 mg) with free combination of the individual drugs in healthy subjects. The pharmacokinetics of vildagliptin and metformin following administration of a fixed-dose combination tablet of vildagliptin/metformin at doses of 50/500 mg (Study I), 50/850 mg (Study II) and 50/1,000 mg (Study III) compared with administration of the individual drugs as free combinations were investigated. All three studies were open-label, single-center, randomized, two-period, two-treatment crossover studies in healthy subjects. Pharmacokinetic parameters (AUC(0-infinity), C(max), t(max), t(1/2) and CL/F) for vildagliptin and metformin across the three studies were similar whether vildagliptin and metformin were administered as a single fixed-dose combination tablet (vildagliptin/metformin 50/500, 50/850 or 50/1,000 mg) or as the respective individual tablets. The point estimates and 90% CI of the geometric mean ratios for vildagliptin and metformin C(max), AUC(0-t), and AUC(0-infinity) were all within the predefined bioequivalence range of 0.80 - 1.25. Administration of the vildagliptin/metformin combination tablets was well tolerated; the incidence of adverse events was similar to that observed with the respective free combinations of vildagliptin and metformin, and the most common individual adverse events were mild gastrointestinal events, which are commonly observed with metformin treatment. The fixed-dose combination tablet of vildagliptin/metformin is bioequivalent to administration of the individual drugs as a free combination at dose levels of 50/500, 50/850 and 50/1,000 mg and is well tolerated. Consequently, the fixed-dose combination tablets are considered therapeutically equivalent and exchangeable to the free combination in clinical practice. Furthermore, the fixed-dose combination tablets are expected to enhance convenience and thereby improve
Full Text Available Aspirin is apt to hydrolyze. In order to improve its stability, a new method has been developed involving the application of hot-melt sub- and outercoating combined with enteric aqueous coating. The main aim was to investigate the influence of these factors on the stability of ASA and understand how they work. Satisfactory storage stability were obtained when the aspirin tablet core coated with Eudragit L30D55 film was combined with glycerin monostearate (GMS as an outercoat. Hygroscopicity testing indicated that the moisture penetrating into the tablet may result in a significant change in the physical properties of the coating film observed by scanning electron microscopy. Investigation of the compatibility between the drug and film excipients shows that the talc and methacrylic acid had a significant catalytic effect on ASA. A hypothesis was proposed that the hydrolysis of ASA enteric coated tablets (ASA-ECT was mostly concentrated in the internal film and the interfaces between the film and tablet core. In conclusion, hot-melt coating technology is an alternative to subcoating or outercoating. Also, GMS sub-coating was a better choice for forming a stable barrier between the tablet core and the polymer coating layer, and increases the structure and chemical stability.
Suganthi A; John Sofiya; Ravi.T
A simple, precise, sensitive, rapid and reproducible HPTLC method for the simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets was developed and validated. This method involves separation of the components by TLC on precoated silica gel G60F254 plate with solvent system of n-butanol, toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out densitometrically using a UV detector at 288 nm in absorbance mode. This system was found to give compact spots for ...
Pathak, A; Rajput, S J
A stability-indicating high-performance liquid chromatography method is developed for analysis of olanzapine and fluoxetine in the presence of their degradation products generated from forced decomposition studies as prescribed by the International Conference on Harmonization. Hydrolysis, oxidation, photolysis, and thermal degradation are evaluated by subjecting the drug substances to stress conditions. Successful separation of drugs from degradation products is achieved on a reversed-phase C(18) column using 75 mM potassium dihydrogen phosphate buffer (pH 4.0)-acetonitrile-methanol (55:40:5, v/v/v) as the mobile phase. The flow rate is 0.8 mL/min, and the detection wavelength is 227 nm. The method is validated with respect to linearity, precision, accuracy, system suitability, and robustness. The utility of the procedure is verified by its application to marketed formulations that are subjected to accelerated stability studies. Good separation of the drugs and their degradation products is observed using this method. The products formed in marketed tablet dosage forms are similar to those formed in standard drug solutions under similar stress conditions.
Combination of ibuprofen and paracetamol is one type of combination in tablet antipyretic-analgesic and anti-inflamatory, that can result potentiation effects to relieve pain, reduce fever and inflamation. The purpose of this research is to find alternative methods of determine the amount of a mixture ibuprofen and paracetamol in tablet dosage using volumetric An alternative method used in determining the amount of ibuprofen in alkalimetry with titrant sodium hydroxide solution, paracetamo...
Elena Gabriela Oltean,
Full Text Available An isocratic high-performance liquid chromatography (HPLC procedure was developed for the quantitative determination of metronidazole in tablets and powders. HPLC separation was carried out by reversed phasechromatography on Kromasil C18 (250 mm x 4.6 mm i.e.; 5 ìm particle size, held in thermostat at 25°C. The mobile phase consisted of methanol/ 0.1% phosphoric acid aq. (20/80v/v, with a flow rate of 1 ml/min and with UV detection at 317 nm. In order to validate the method, the following parameters have been investigated: linearity (r2=0.9999, range, precision, accuracy, specificity, limit of detection and limit of quantification. The described method can be successfully applied for the analysis of the active pharmaceuticalcompound in tablets and powders. This paper aimed to develop and validate an HPLC sensitive applicable method to determine the quantity of metronidazole in tablets and powders, contributing to the quality and safety control of these types of pharmaceutical preparations.
Pathak, A.; Rajput, S. J.
Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot's method) were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 μg/ml, 1-40 μg/ml and 1-30 μg/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations. PMID:20046784
Syamala, Urmila Sri; Kumar, Raman Suresh; Pushkarajan, Tambi Anuj; Gowthamarajan, Kuppuswamy
A model immunosuppressant BCS Class II drug was selected for the work to assess the formulation variables on the release rate using design of experiment (DoE) - Stat-Ease software. Surface solid dispersion was prepared with dichloromethane (DCM) and ethanol mixture (4:1), and converted to tablet by adsorption on a neutral carrier. Different batches were prepared with DoE full factorial design. The concentrations of Polaxamer 188, Kollidon CL and magnesium stearate were found to be the critical factors affecting the performance of the tablets. These parameters were selected as the independent variables in DoE and the formulated batches were evaluated for their percentage release at 120 minutes. The actual and predicted plots fall close to the line. ANOVA (partial sum squares-type-III) reveals the model with F-value of 1417.12 which implies significant. The optimized batch with dissolution profile of 99.6% falls close to the innovator product 98.8%.
Gupta, M. M.; Gupta, Niraj; Chauhan, Bhupendra S.; Pandey, Shweta
The aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride and Montelukast sodium by using direct compression method. To prevent bitter taste and unacceptable odour of the Levocetrizine dihydrochloride drug, the drug was taste masked with ion exchange resins like Kyron-T-104 and Tulsion-412. Among the two resins, Kyron-T-104 was selected for further studies because of high drug loading capacity, low cost, and better drug release profile. An ion exchange resin complex was prepared by the batch technique and various parameters; namely, resin activation, drug: resin ratio, pH, temperature, and stirring time, and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC). The tablets were prepared using microcrystalline cellulose (MCC) PH 102 as diluent along with crospovidone (CP), croscarmellose sodium (CCM), and sodium starch glycolate (SSG) as a superdisintegrants. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT), and dissolution study and it was concluded that the tablet formulation prepared with 2% SSG + CCS showed better disintegration time in comparison with other formulation and good drug release. The stability studies were carried out for the optimized batch for three months and it showed acceptable results. PMID:26556198
M. M. Gupta
Full Text Available The aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride and Montelukast sodium by using direct compression method. To prevent bitter taste and unacceptable odour of the Levocetrizine dihydrochloride drug, the drug was taste masked with ion exchange resins like Kyron-T-104 and Tulsion-412. Among the two resins, Kyron-T-104 was selected for further studies because of high drug loading capacity, low cost, and better drug release profile. An ion exchange resin complex was prepared by the batch technique and various parameters; namely, resin activation, drug: resin ratio, pH, temperature, and stirring time, and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC. The tablets were prepared using microcrystalline cellulose (MCC PH 102 as diluent along with crospovidone (CP, croscarmellose sodium (CCM, and sodium starch glycolate (SSG as a superdisintegrants. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT, and dissolution study and it was concluded that the tablet formulation prepared with 2% SSG + CCS showed better disintegration time in comparison with other formulation and good drug release. The stability studies were carried out for the optimized batch for three months and it showed acceptable results.
Gupta, M M; Gupta, Niraj; Chauhan, Bhupendra S; Pandey, Shweta
The aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride and Montelukast sodium by using direct compression method. To prevent bitter taste and unacceptable odour of the Levocetrizine dihydrochloride drug, the drug was taste masked with ion exchange resins like Kyron-T-104 and Tulsion-412. Among the two resins, Kyron-T-104 was selected for further studies because of high drug loading capacity, low cost, and better drug release profile. An ion exchange resin complex was prepared by the batch technique and various parameters; namely, resin activation, drug: resin ratio, pH, temperature, and stirring time, and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC). The tablets were prepared using microcrystalline cellulose (MCC) PH 102 as diluent along with crospovidone (CP), croscarmellose sodium (CCM), and sodium starch glycolate (SSG) as a superdisintegrants. The tablets were evaluated for weight variation, hardness, friability, wetting time, water absorption ratio, disintegration time (DT), and dissolution study and it was concluded that the tablet formulation prepared with 2% SSG + CCS showed better disintegration time in comparison with other formulation and good drug release. The stability studies were carried out for the optimized batch for three months and it showed acceptable results.
Zikán, V; Roubal, P; Stĕpán, J
The aim of this study was to assess acute biochemical changes after the administration of two different pharmaceutical forms of calcium carbonate or milk. The group of 12 young (aged 20-27 years) and 12 older women (aged 63-71 years). After overnight fasting, each of the volunteers received a 1 g of elemental calcium in either form of the tested preparation: powder form of calcium carbonate--Vitacalcin pulvis (Slovakofarma, SR) or effervescent tablet--Calcium 500 mg Pharmavit (Pharmavit, MR) or in 250 ml of milk enriched with the milk calcium complex. Between each test the interval of 1-2 weeks was held. Samples of blood and urine were taken in the fasting state before and during 5.5 h following ingestion of the calcium load. Both calcium carbonate and milk induced a significant increase in the serum ionised calcium (iCa) and a significant decrease in plasma parathormone level (PTH) in comparison with the baseline levels in both groups of women. Comparison between individual preparations and between preparations and milk did not reveal any significant differences in suppression of PTH. Comparison of the effects between young and elderly women did not show any statistically significant difference in any measured parameter. Our results confirmed the good bioavailability of calcium from milk and from both calcium preparations in both age groups of women. Significantly more frequent hypercalcemia in the young women (p effervescent tablet than after the application of calcium in the form of powder or after the application of milk.
Shahid S. Chaudhary; Mohd. Tariq; Roohi Zaman; Shaikh Imtiyaz
Drugs obtained from natural sources are rarely administered or dispensed to patients in their native forms but are formulated into dosage forms. In Unani system of medicine dosage forms are broadly classified into four categories according to their state these are solid dosage forms, semisolid, liquid and gaseous dosage forms. Among them solid dosage forms e.g. Sufoof (powder), Kohal (coryllium), Kushta (calx), Qurs (tablet) etc have several advantages over other dosage forms such as higher s...
B. V. Suma
Full Text Available A new simple, specific, precise and accurate revere phase liquid chromatography method has been developed for estimation of atorvastatin calcium (AST and ASPIRIN (ASP simultaneously in a combined capsule dosage forms. The chromatographic separation was achieved on a 5 – micron C 18 column (250x 4.6mm using a mobile phase consisting of a mixture of Acetonitrile: Ammonium Acetate buffer 0.02M (68:32 pH 4.5. The flow rate was maintained at 0.8 ml/min. The detection of the constituents was done using UV detector at 245 nm for AST and ASP. The retention time of AST and ASP were found be 4.5915 ± 0.0031 min and 3.282 ±0.0024 min respectively. The developed method was validated for accuracy, linearity, precision, limit of detection (LOD and limit of quantification (LOQ and robustness as per the ICH guidelines.
Full Text Available Intestinal infection (II of various etiologies is among to the most widespread diseases in the world. The treatment regimen bacterial etiology involves the suppression of pathogenic and conditionally pathogenic with the restoration of the normal intestinal microflora. For effective antibiotic pharmacotherapy of intestinal infections are widely used drug combinations with the additionof nifuroxazide, as well as enzymatic and normalizing bowel motility broad-spectrum drugs. Intestinal antiseptics nifuroxazide characterized by broad spectrum of antibacterial action against Staphylococcus spp, Clostridium spp, E. coli, Salmonella spp, Shigellaspp, Proteus spp, Klebsiellaspp, Enterobacter spp, V. cholerae, H. pylori, Yersinia spp, and also the lack of effect on the normal intestinal flora, high safety profile. Recently, for the treatment of intestinal infections nifuroxazide often combined with pre- and probiotics for complex correction of the intestinal microflora disorders. For complex therapy of intestinal infections, we have developed an original combined medicine "Diaplant", in the form of capsules, comprising as active ingredients nifuroxazide (200 mg in combination with plant substance plantaglucide (200 mg. Plantaglucide drug obtained from Plantago major has spasmolytic, antimicrobial and anti-inflammatory activity, normalizes bowel peristalsis, while reducing the tone of smooth muscles of the stomach and intestines, reduces swelling folds of the gastric mucosa, and contained therein polysaccharides in the form of pectins have properties of prebiotic and have immunostimulatory effects. Aim of the work – study of antibacterial action of combined drug "Diaplant" containing nifuroxazide and plantaglucide in regard to test strains and clinical strains of microorganisms allocated from patients with bacterial diarrhea. Materials and methods. Estimation of antimicrobial activity was performed under conditions in vitro by method of serial dilutions
Genina, Natalja; Boetker, Johan Peter; Colombo, Stefano
The design and production of an oral dual-compartmental dosage unit (dcDU) was examined in vitro and in vivo with the purpose of physically isolating and modulating the release profile of an anti-tuberculosis drug combination. Rifampicin (RIF) and isoniazid (ISO) are first line combination drugs...
Full Text Available A simple, rapid, selective and reproducible reversed-phase high performance liquid chromatographic (RP-HPLC method has been developed and validated for the estimation of release of Candesartan cilexetil (CC in tablets. Analysis was performed on an Agilent, Zorbax C8 column (150mm × 4.6mm, 5μm with the mobile phase consisting of phosphate buffer (pH2.5–acetonitrile (15:85, v/v at a flow rate of 1.0mL/min. UV detection was performed at 215nm and the retention time for CC was 2.2. The calibration curve was linear (correlation coefficient = 1.000 in the selected range of analyte. The optimized dissolution conditions include the USP apparatus 2 at a paddle rotation rate of 50rpm and 900mL of phosphate buffer (pH7.2 with 0.03% of polysorbate 80 as dissolution medium, at 37.0 ± 0.5°C. The method was validated for precision, linearity, specificity, accuracy, limit of quantitation and ruggedness. The system suitability parameters, such as theoretical plate, tailing factor and relative standard deviation (RSD between six standard replicates were well within the limits. The stability result shows that the drug is stable in the prescribed dissolution medium. Three different batches (A, B and C of the formulation containing 8mg of Candesartan cilexetil was performed with the developed method and the results showed no significant differences among the batches.
Full Text Available A simple and sensitive thin-layer chromatographic method has been established for analysis of rasagiline mesylate in pharmaceutical dosage form. Chromatography on silica gel 60 F254 plates with 6 : 1 : 2(v/v/v butanol-methanol water as mobile phase furnished compact spots at Rf 0.76±0.01. Densitometric analysis was performed at 254 nm. To show the specificity of the method, rasagiline mesylate was subjected to acid, base, neutral hydrolysis, oxidation, photolysis, and thermal decomposition, and the peaks of degradation products were well resolved from that of the pure drug. Linear regression analysis revealed a good linear relationship between peak area and amount of rasagiline mesylate in the range of 100–350 ng/band. The minimum amount of rasagiline mesylate that could be authentically detected and quantified was 11.12 and 37.21 ng/band, respectively. The method was validated, in accordance with ICH guidelines for precision, accuracy, and robustness. Since the method could effectively separate the drug from its degradation products, it can be regarded as stability indicating.
Raghuvanshi, R S; Tripathi, K P; Jayaswal, S B; Singh, J
Microcapsules of salbutamol sulphate were prepared using beeswax and carnauba wax as coating materials. In vitro release kinetics were studied following the zero order, first order and Higuchi equations. Beeswax alone was not effective but beeswax and carnauba wax combinations were suitable in controlling the in vitro release of the drug. Microcapsules were compressed into tablets to get a controlled release oral dosage form. Release from tableted microcapsules was significantly more prolonged than the respective batches of the microcapsules. Best data fit with the highest correlation coefficient for the tableted microcapsules was obtained for first order.
Development and Validation of a Stability-Indicating Capillary Electrophoresis Method for the Determination of Zolpidem Tartrate in Tablet Dosage Form with Positive Confirmation using 2D- and 3D-DAD Fingerprints.
Al Azzam, Khaldun M; Yit, Lee Kam; Saad, Bahruddin; Shaibah, Hassan
The aim of the current study was to develop a simple, precise, and accurate capillary zone electrophoresis method for the determination of zolpidem tartrate in tablet dosage form. Separation was conducted in normal polarity mode at 25°C, 22 kV, using hydrodynamic injection for 10 s. Separation was achieved using a background electrolyte of 20 mM disodium hydrogen phosphate adjusted with phosphoric acid (85%), pH at 5.50, and detection at 254 nm. Using the above optimized conditions, complete determination took place in less than 3 min using amiloride HCl as the internal standard. The method was linear over the range of 3-1000 μg mL(-1) with a correlation coefficient of 0.9999. Forced degradation studies were conducted by introducing a sample of zolpidem tartrate standard and pharmaceutical sample solutions to different forced degradation conditions, being neutral (water), basic (0.1 M NaOH), acidic (0.1 M HCl), oxidative (10% H2O2), temperature (60°C in oven for 3 days), and photolytic (exposure to UV light at 254 nm for 2 h). Degradation products resulting from the stress studies did not interfere with the detection of zolpidem tartrate and the assay can be considered stability-indicating.
Genina, Natalja; Fors, Daniela; Vakili, Hossein
We combined conventional inkjet printing technology with flexographic printing to fabricate drug delivery systems with accurate doses and tailored drug release. Riboflavin sodium phosphate (RSP) and propranolol hydrochloride (PH) were used as water-soluble model drugs. Three different paper...... substrates: A (uncoated woodfree paper), B (triple-coated inkjet paper) and C (double-coated sheet fed offset paper) were used as porous model carriers for drug delivery. Active pharmaceutical ingredient (API) containing solutions were printed onto 1 cm × 1 cm substrate areas using an inkjet printer....... The printed APIs were coated with water insoluble polymeric films of different thickness using flexographic printing. All substrates were characterized with respect to wettability, surface roughness, air permeability, and cell toxicity. In addition, content uniformity and release profiles of the produced...
Nada S. Abdelwahab
In Method (I, two wavelengths were selected for each drug in such a way that the difference in absorbance is zero for the second drug. At wavelengths 238 and 248.8 nm HCT has equal absorbance values, therefore, these two wavelengths have been used to determine CV, on similar basis 266 and 289.4 nm were selected to determine HCT in the combined formulation. Method (II involves the formation of Q-absorbance equation using the respective absorptivity values at 229.2 nm (isoabsorptive point and 241 nm (λmax of CV. The drugs obey Beer’s Lambert’s law in the concentration range of 1–10 μg/mL for both CV and HCT (for Method I and in the range of 1–10 and 2–10 μg/mL for CV and HCT, respectively (for Method II. The accuracy and precision were determined and recovery studies confirmed the accuracy of the developed methods that were carried out following the International Conference on Harmonization (ICH guidelines. Statistical comparison of the suggested methods with the reported spectrophotometric one using F and t tests showed no significant difference regarding both accuracy and precision.
Development of two step liquid-liquid extraction tandem UHPLC-MS/MS method for the simultaneous determination of Ginkgo flavonoids, terpene lactones and nimodipine in rat plasma: Application to the pharmacokinetic study of the combination of Ginkgo biloba dispersible tablets and Nimodipine tablets.
Xiao, Jie; Wang, Tianyang; Li, Pei; Liu, Ran; Li, Qing; Bi, Kaishun
A sensitive, reliable and accurate UHPLC-MS/MS method has been firstly established and validated for the simultaneous quantification of ginkgo flavonoids, terpene lactones and nimodipine in rat plasma after oral administration of Ginkgo biloba dispersible tablets, Nimodipine tablets and the combination of the both, respectively. The plasma samples were extracted by two step liquid-liquid extraction, nimodipine was extracted by hexane-ether (3:1, v/v) at the first step, after that ginkgo flavonoids and terpene lactones were extracted by ethyl acetate. Then the analytes were successfully separated by running gradient elution with the mobile phase consisting of 0.1% formic acid in water and methanol at a flow rate of 0.6mL/min. The detection of the analytes was performed on a UHPLC-MS/MS system with turbo ion spray source in the negative ion and multiple reaction monitoring (MRM) mode. The calibration curves for the determination of all the analytes showed good linearity (R(2)>0.99), and the lower limits of quantification were 0.50-4.00ng/mL. Intra-day and inter-day precisions were in the range of 3.6%-9.2% and 3.2%-13.1% for all the analytes. The mean extraction recoveries of the analytes were within 69.82%-103.5% and the matrix were within 82.8%-110.0%. The validated method had been successfully applied to compare the pharmacokinetic parameters of ginkgo flavonoids, terpene lactones and nimodipine in rat plasma after oral administration of Ginkgo biloba dispersible tablets, Nimodipine tablets with the combination of the both. There were no statistically significant differences on the pharmacokinetic behaviors of all the analytes between the combined and single administration groups. Results showed that the combination of the two agents may avoid dosage adjustments in clinic and the combination is more convenient as well as efficient on different pathogenesis of cerebral ischemia. Copyright © 2016 Elsevier B.V. All rights reserved.
Pharmacists who are engaged in drug compounding have specific guidelines and standards that are outlined in the United States Pharmacopeia-National Formulary. Of the many dosage forms that are available for the compounder, capsules and tablets (peroral solids) represent the most stable and convenient formulations for drug combinations. Dosage units must remain consistent, and the uniformity of dosage units should be demonstrable. Specific standards for the uniformity of dosage units are outlined in United States Pharmacopeia Chapter 905, which was developed specifically for the pharmaceutical industry. The uniformity of dosage units can be demonstrated by either of two methods, Content Uniformity or Weight Variation. Weighing and blending activities are critical in compounding. Therefore, all efforts should be expended to prevent errors in weighing and other steps that could adversely affect the final preparation.
Chalitpon Na nakorn
Full Text Available Alendronate is indicated for treatment of a variety of bone metabolism disorders. In spite of quite low plasma concentrationsfollowing oral administration, pharmacokinetic study of alendronate based on plasma concentrations had normally been reported for up to 8 h. Due to much longer detectable periods in urine, a number of pharmacokinetic studies have been based upon urinary excretion data. The objective of this study was to determine pharmacokinetics of alendronate following oral administration of combined Alendronate/Vitamin D3 tablet. Blood and urine samples were collected for 10 h after oral administration of a combined Alendronate/Vitamin D3 tablet to healthy volunteers. Alendronate levels in plasma and urine samples were determined by high-performance liquid chromatography (HPLC with fluorescence detection. The analytical method involved co-precipitation of alendronate in plasma or urine samples with calcium and followed by solid-phase extraction (SPE process. Pharmacokinetic parameters were analyzed by the non-compartmental method using WinNonlin. Pharmacokinetics parameters, i.e. Cmax, Tmax, AUC0-10, T1/2, were 56.6±11.8 ng/mL, 1.29±0.39 h, 132.4±46.9 ng·h/mL, and 3.43±2.24 h,respectively. Amount excreted in 10 h urine and maximum excretion rate (Rmax were 578.59±308.9 μg and 143.3±72.8 μg/h, respectively. Although these parameters were different from previously reported values, Rmax obtained at 1.29±0.76 h agreed well with Tmax observed from plasma data. Based upon urinary excretion data, enhanced absorption of alendronate after administration of a combined Alendronate/Vitamin D3 tablet is suggested.
Sunaric, Slavica; Petkovic, Milica; Denic, Marko; Mitic, Snezana; Pavlovic, Aleksandra
Solid-phase extraction method followed by direct UV spectrophotometry at 264 nm was developed and applied for the selective ibuprofen determination in two-component formulation of ibuprofen and pseudoephedrine-HCl, combined powder which contains ibuprofen in the form of salt with L-arginine and 10% ibuprofen cream. Procedures for ibuprofen determination in complex pharmaceutical preparations by direct UV spectrophotometry lack selectivity because of interferences of other active substances and fat components. A limited number of spectrophotometric methods applicable to these samples are based on derivative (first and second-order) UV spectroscopy. Common HPLC procedures are more selective but more expensive and for creams also require some type of extraction because the large amount of oily excipients would clog up the column. The proposed solid-phase extraction method proved to be suitable for analysis of ibuprofen in combined tablets, powders and creams by direct UV spectrophotometry. Also the method provides an effective clean-up of the cream and allows ibuprofen determination by HPLC analysis. For the extraction three different commercial sorbents were tested: anion exchange Oasis MAX, hydrophilic-lipophilic balanced Oasis HLB and reverse-phase Chromabond C18ec. The optimization of the SPE method was first done on standard ibuprofen solutions and then the suitability of the method was checked on solutions of commercial pharmaceutical samples. The method yields good results for all three types of commercial preparations on the anion-exchange Oasis MAX cartridges, with recoveries of 90-100.2%. The interferences in UV analysis were not registered and good precision (RSD < 6%) was obtained. The present method has been verified as accurate as the reference HPLC with the great advantage of less expensive instrumentation. For this reason, the method would be suitable for a routine and rapid drug quality control.
Full Text Available AIM: To observe the clinical curative effect of calcium dobesilate capsule and yimaikang tablet for treating retinal vein occlusion(RVO. METHODS:A total of 120 patients(167 eyeswith RVO were divided into 2 groups at random. The control group of 60 cases(82 eyeswere given calcium dobesilate capsule, and the treatment group of 60 cases(85 eyesreceived calcium dobesilate capsule and yimaikang tablet. Changes of visual acuity and clinical effects after 3 courses of treatment were compared and analyzed for all patients. RESULTS: Markedly effective 15 cases(23 eyes, effective 42 cases(57 eyesand invalid 3 cases(5 eyesin the 60 cases(85 eyesof the treatment group, the total effective rate was 94.1%. Eighty-two eyes of 60 cases in the control group, markedly effective in 8 cases(12 eyes, effective 38 cases(49 eyes, ineffective 14 cases(21 eyes, The total effective rate was 74.4% in the control group. There were significant differences between the 2 groups of curative effect, and low incidence rate of adverse reaction. CONCLUSION: Calcium dobesilate capsules and yimaikang tablet is effective and safe in the treatment of RVO.
Haggag, Rim S; Shaalan, Rasha A; Belal, Tarek S
Simple, rapid, and selective RP-HPLC methods with UV detection were developed for simultaneous determination of chlordiazepoxide hydrochloride and mebeverine hydrochloride (Mixture I) and carvedilol and hydrochlorothiazide (Mixture II). The chromatographic separation in both mixtures was achieved by using an RP-C8 (octylsilyl) analytical column. For Mixture I, a mobile phase composed of acetonitrile-0.05 M disodium hydrogen phosphate-triethylamine (50 + 50 + 0.2, v/v/v), pH 2.5, was used; the detector wavelength was 247 nm. For Mixture II, the mobile phase consisted of acetonitrile-0.05 M disodium hydrogen phosphate (50 + 50, v/v), pH 4.0, and the detector was set at 220 nm. Quantification of the analytes was based on measuring their peak areas. Both mixtures were resolved in less than 6 min. The reliability and analytical performance of the proposed HPLC procedures were statistically validated with respect to linearity, range, precision, accuracy, selectivity, robustness, LOD, and LOQ. The linear dynamic ranges were 2.5-150 and 2.5-500 microg/mL for chlordiazepoxide HCI and mebeverine HCI, respectively, and 0.25-200 and 0.25-150 microg/mL for carvedilol and hydrochlorothiazide, respectively. The validated HPLC methods were successfully applied to the analysis of their commercial tablet dosage forms, for which no interfering peaks were encountered from common pharmaceutical adjuvants.
Vojta, Jiří; Hanzlík, Pavel; Jedlička, Aleš; Coufal, Pavel
A new HPLC method for separation and determination of impurities in paracetamol, codeine phosphate hemihydrate and pitophenone hydrochloride in the presence of fenpiverinium bromide in combined suppository dosage form was developed and validated. The separation of paracetamol and its impurities 4-aminophenol, 4-nitrophenol, 4-chloracetanilid; codeine and its impurities methylcodeine, morphine, codeine dimer and 10-hydroxycodeine; pitophenone and its impurities 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl] benzoic acid, 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl]benzoic acid 2-(1-piperidinyl)-ethyl ester, methyl ester of 2-(4-hydroxybenzoyl) benzoic acid and fenpiverinium was achieved by using ion-pair reversed phase liquid chromatography with UV detection. Validation parameters such as the precision, accuracy, linearity, limit of detection (LOD), limit of quantification (LOQ) and robustness were verified for all the mentioned impurities of codeine phosphate hemihydrate and 4-aminophenol and 2-[4-[2-(1-piperidinyl)ethoxy]benzoyl] benzoic acid as the main degradation products of paracetamol and pitophenone hydrochloride, respectively. The described method was found to be useful for analysis of the stability samples and therefore suitable for routine purity testing of the drug product. Copyright © 2014 Elsevier B.V. All rights reserved.
Full Text Available A simple, precise, rapid, and economic method was developed for the simultaneous determination of Ibuprofen and Phenylephrine HCl in bulk and combined dosage form. This method involves first-order derivative spectroscopy using 248 nm and 237 nm as zero crossing points for Ibuprofen and Phenylephrine HCl, respectively. For spectrophotometric method 0.1 N NaOH was used as a solvent. The linearity was established over the concentration range of 12–72 μg/mL and 1.5–22 μg/mL for Ibuprofen and Phenylephrine HCl with correlation coefficient (r2 of 0.9972 and 0.9981, respectively. The mean % recoveries were found to be in the range of 98.88% and 98.54% for Ibuprofen and Phenylephrine HCl, respectively. Interday and intraday studies showed repeatability of the method. The method was found to be specific and robust. The method was successfully applied to pharmaceutical formulation, with no interference from excipients as indicated by the recovery study. Results of analysis were validated statistically and by recovery studies.
Ragab, Mona T; Abd El-Rahman, Mohamed K; Ramadan, Nesrin K; El-Ragehy, Nariman A; El-Zeany, Badr A
Three sensitive and selective polyvinyl chloride (PVC) matrix membrane electrodes were developed and investigated. Sensor I was developed using tetraheptylammonium bromide (THB) as an anion exchanger with 2-nitrophenyl octyl ether (2-NPOE) as a plasticizer for the determination of the anionic drug pantoprazole sodium sesquihydrate (PAN). To determine the cationic drug itopride hydrochloride (ITH), two electrodes (sensors II and III) were developed using potassium tetrakis(4-chlorophenyl) borate (KTCPB) as a cation exchanger with dioctyl phthalate (DOP) as a plasticizer. Selective molecular recognition components, 2-hydroxypropyl-β-cyclodextrin (2-HP βCD) and 4-tert-butylcalixarene (tBC8), were used as ionophores to improve the selectivity of sensors II and III, respectively. The proposed sensors had a linear dynamic range of 1×10(-5) to 1×10(-2) mol L(-1) with Nernstian slopes of -54.83±0.451, 56.90±0.300, and 51.03±1.909 mV/decade for sensors I, II and III, respectively. The Nernstian slopes were also estimated over the pH ranges of 11-13, 3.5-8 and 4-7 for the three sensors, respectively. The proposed sensors displayed useful analytical characteristics for the determination of PAN and ITH in bulk powder, in laboratory prepared mixtures and in combined dosage forms with clear discrimination from several ions, sugars and some common drug excipients. The method was validated according to ICH guidelines. Statistical comparison between the results from the proposed method and the results from the reference methods showed no significant difference regarding accuracy and precision. Copyright © 2015 Elsevier B.V. All rights reserved.
Full Text Available A sensitive and precise RP-HPLC method has been developed for the simultaneous estimation of clidinium bromide (CDB and chlordiazepoxide (CDZ in pure and pharmaceutical formulations. The separation was achieved on a Nucleodur C8 ( mm i.d., 5 μm particle size column at 25°C. CH3CN-MeOH-NH4OAc 0.1M (30 : 40 : 30, v/v/v was used as the mobile phase at a flow rate of 1.0 mL min−1 and detector wavelength at 218 nm. Almotriptan (ALT was used as internal standard. The validation of the proposed method was carried out for linearity, accuracy, precision, LOD, LOQ, and robustness. The method showed good linearity in the ranges of 2.5–300.0 and 3.0–500.0 μg mL−1 for CDB and CDZ, respectively. The percentage recovery obtained for CDB and CDZ was 100.40–103.38 and 99.98–105.59%, respectively. LOD and LOQ were 0.088 and 0.294 μg mL−1 for CDB and 0.121 and 0.403 μg mL−1 for CDZ, respectively. The proposed method was successfully applied to the determination of CDB and CDZ in combined dosage forms and the results tallied well with the label claim.
Doherty, Michael; Hawkey, Chris; Goulder, Michael; Gibb, Iain; Hill, Nicola; Aspley, Sue; Reader, Sandie
To compare the efficacy and safety of single versus combination non-prescription oral analgesics in community-derived people aged 40 years and older with chronic knee pain. A randomised, double-blind, four-arm, parallel-group, active controlled trial investigating short-term (day 10) and long-term (week 13) benefits and side-effects of four regimens, each taken three times a day: ibuprofen (400 mg); paracetamol (1000 mg); one fixed-dose combination tablet (ibuprofen 200 mg/paracetamol 500 mg); two fixed-dose combination tablets (ibuprofen 400 mg/paracetamol 1000 mg). There were 892 participants (mean age 60.6, range 40-84 years); 63% had radiographic knee osteoarthritis and 85% fulfilled American College of Rheumatology criteria for osteoarthritis. At day 10, two combination tablets were superior to paracetamol (pparacetamol (p=0.015, p=0.0002, respectively; n=615). The frequency of adverse events was comparable between groups. However, by 13 weeks, decreases in haemoglobin (≥1 g/dl) were observed in some participants in all groups. Twice as many participants taking two combination tablets had this decrease compared with those on monotherapy (pparacetamol, 20.3%; ibuprofen, 19.6%; one or two combination tablets, 24.1%, 38.4%, respectively). Ibuprofen/paracetamol combination analgesia, at non-prescription doses, confers modest short-term benefits for knee pain/osteoarthritis. However, in this population, paracetamol 3 g/day may cause similar degrees of blood loss as ibuprofen 1200 mg/day, and the combination of the two appears to be additive. Study no ISRCTN77199439.
Wang, Xiao-lin; Liu, Man; Yang, Man; Zhang, Ya-nan; Zhang, Dan; Zhang, Li-na; Han, Jing; Liu, Hui-chen
The gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin were evaluated in healthy Chinese volunteers. Thirty-six healthy male and female volunteers were enrolled in the study receiving a single oral dose of niacin extended-release/simvastatin 1,000/20 mg. The results indicated that the systemic exposure of simvastatin hydroxy acid and the total urine excretion of niacin were significantly higher for females compared with those for males, and the T max of niacin in plasma was significantly shorter for males than that for females. There were no significant differences in the systemic exposure of simvastatin, niacin, and NUA in plasma between males and females.
transfer complexes. The complexes obtained were measured spectrophotometrically at 292, 220, 520,. 302, and 824 nm for I2, CH, ... [13,14], which absorb radiation in both ultra-violet and visible region. The rapid formation of the ... A double beam ultraviolet-visible spectro- photometer (Thermo Scientific, England) with 1-.
Formulation design of double-layer in the outer shell of dry-coated tablet to modulate lag time and time-controlled dissolution function: Studies on micronized ethylcellulose for dosage form design (VII)
Lin, Shan-Yang; Lin, Kung-Hsu; Li, Mei-Jane
... the release behavior of sodium diclofenac from dry-coated tablet were also explored. The results indicate that sodium diclofenac released from all the dry-coated tablets exhibited an initial lag period, followed by a stage of rapid drug release...
Singh, Veena D.; Daharwal, Sanjay J.
Three multivariate calibration spectrophotometric methods were developed for simultaneous estimation of Paracetamol (PARA), Enalapril maleate (ENM) and Hydrochlorothiazide (HCTZ) in tablet dosage form; namely multi-linear regression calibration (MLRC), trilinear regression calibration method (TLRC) and classical least square (CLS) method. The selectivity of the proposed methods were studied by analyzing the laboratory prepared ternary mixture and successfully applied in their combined dosage form. The proposed methods were validated as per ICH guidelines and good accuracy; precision and specificity were confirmed within the concentration range of 5-35 μg mL- 1, 5-40 μg mL- 1 and 5-40 μg mL- 1of PARA, HCTZ and ENM, respectively. The results were statistically compared with reported HPLC method. Thus, the proposed methods can be effectively useful for the routine quality control analysis of these drugs in commercial tablet dosage form.
Full Text Available A simple, rapid and reproducible HPLC method was developed for the simultaneous determination of amlodipine and valsartan in their combined dosage forms, and for drug dissolution studies. A C18 column (ODS 2, 10 μm, 200 x 4.6 mm and a mobile phase of phosphate buffer (pH 3.6 , 0.01 mol L-1:acetonitrile: methanol (46:44:10 v/v/v mixture were used for separation and quantification. Analyses were run at a flow-rate of 1 mL min-1 and at ambient temperature. The injection volume was 20 μL and the ultraviolet detector was set at 240 nm. Under these conditions, amlodipine and valsartan were eluted at 7.1 min and 3.4 min, respectively. Total run time was shorter than 9 min. The developed method was validated according to the literature and found to be linear within the range 0.1 - 50 μg mL-1 for amlodipine, and 0.05 - 50 μg mL-1 for valsartan. The developed method was applied successfully for quality control assay of amlodipine and valsartan in their combination drug product and in vitro dissolution studies.Desenvolveu-se método de HPLC rápido e reprodutível para a determinação simultânea de anlodipino e valsartana em suas formas de associação e para os estudos de dissolução dos fármacos. Utilizaram-se coluna C18 (ODS 2, 10 μm, 200 x 4,6 mm e fase móvel tampão fosfato (pH 3,6, 0,01 mol L-1:acetonitrila: metanol para a separação e a quantificação. As análises foram efetuadas com velocidade de fluxo de 1 mL min-1 e à temparatura ambiente O volume de injeção foi de 20 μL e utilizou-se detector de ultravioleta a 240 nm. Sob essas condições, anlodipino e valsartana foram eluídas a 7,1 min e 3,4 min, respectivamente. O tempo total de corrida foi menor que 9 min. O método desenvolvido foi validado de acordo com a literatura e se mostrou linear na faixa de 0,1-50 μg mL-1 para anlodipino e de 0,05-50 μg mL-1 para valsartana. O método desenvolvido foi aplicado com sucesso para ensaios de controle de qualidade de associações de
Merckle, P; Kovar, K A
Near-infrared spectroscopy (NIRS) was used to determine acetylsalicylic acid (ASA) in three different effervescent tablet formulations. The nominal ASA concentrations were 14.9% in the single substance formulation (ASA Mono), 17.4% in the combination with ascorbic acid (ASA + C) and 8.7% in the combination with paracetamol and ascorbic acid (ASA Combi). In each case the tablet matrix was composed of seven excipients typical of effervescent tablets. All three formulations were measured as intact tablets in diffuse transmittance and reflectance and as powdered tablets in diffuse reflectance. Calibration was carried out by partial least square (PLS) regression of second derivative spectra. High-performance liquid chromatography (HPLC) was used as the reference method. The relative standard errors of calibration (RSEC) achieved for the three NIR methods were between 1.20 and 2.01% for ASA Mono, between 1.91 and 2.21% for ASA + C and between 2.41 and 4.50% for ASA Combi. The results obtained in transmittance mode were comparable with those obtained in reflectance mode, which is normally used in NIRS. In the test sets of ASA Mono and ASA + C relative root mean square (RRMS) values between 2.21 and 3.13% were obtained. The three NIR methods applied are thus suitable for the quantitative determination of ASA in effervescent tablets and have the advantage over HPLC of being rapid and simply carried out with little sample preparation; they are nondestructive and do not require any environmentally harmful reagents.
Razavi, Mahboubeh; Karimian, Hamed; Yeong, Chai Hong; Chung, Lip Yong; Nyamathulla, Shaik; Noordin, Mohamed Ibrahim
The present research was aimed at formulating a metformin HCl sustained-release formulation from a combination of polymers, using the wet granulation technique. A total of 16 formulations (F1–F16) were produced using different combinations of the gel-forming polymers: tamarind kernel powder, salep (palmate tubers of Orchis morio), and xanthan. Post-compression studies showed that there were no interactions between the active drug and the polymers. Results of in vitro drug-release studies indicated that the F10 formulation which contained 5 mg of tamarind kernel powder, 33.33 mg of xanthan, and 61.67 mg of salep could sustain a 95% release in 12 hours. The results also showed that F2 had a 55% similarity factor with the commercial formulation (C-ER), and the release kinetics were explained with zero order and Higuchi models. The in vivo study was performed in New Zealand White rabbits by gamma scintigraphy; the F10 formulation was radiolabeled using samarium (III) oxide (153Sm2O3) to trace transit of the tablets in the gastrointestinal tract. The in vivo data supported the retention of F10 formulation in the gastric region for 12 hours. In conclusion, the use of a combination of polymers in this study helped to develop an optimal gastroretentive drug-delivery system with improved bioavailability, swelling, and floating characteristics. PMID:26273196
Full Text Available Serge Halimi1, Anja Schweizer2, Biljana Minic2, James Foley3, Sylvie Dejager41University Hospital of Grenoble College of Medicine, Diabetes and Endocrine department, Grenoble, France; 2Novartis Pharma AG, Basel, Switzerland; 3Novartis Pharmaceuticals Corporation, E. Hanover, NJ, 4Novartis Pharmaceuticals Corporation, Rueil Malmaison, FranceAbstract: Vildagliptin is a potent and selective inhibitor of dipeptidyl peptidase-IV (DPP-4, orally active, that improves glycemic control in patients with type 2 diabetes (T2DM primarily by enhancing pancreatic (α and β islet function. Thus vildagliptin has been shown both to improve insulin secretion and to suppress the inappropriate glucagon secretion seen in patients with T2DM. Vildagliptin reduces HbA1c when given as monotherapy, without weight gain and with minimal hypoglycemia, or in combination with the most commonly prescribed classes of oral hypoglycemic drugs: metformin, a sulfonylurea, a thiazolidinedione, or insulin. Metformin, with a different mode of action not addressing β-cell dysfunction, has been used for about 50 years and still represents the universal first line therapy of all guidelines. However, given the multiple pathophysiological abnormalities in T2DM and the progressive nature of the disease, intensification of therapy with combinations is typically required over time. Recent guidelines imply that patients will require pharmacologic combinations much earlier to attain and sustain the increasingly stringent glycemic targets, with careful drug selection to avoid unwanted adverse events, especially hypoglycemia. The combination of metformin and vildagliptin offers advantages when compared to currently used combinations with additive efficacy and complimentary mechanisms of action, since it does not increase the risk of hypoglycemia and does not promote weight gain. Therefore, by specifically combining these agents in a single tablet, there is considerable potential to achieve
Nikam, A. D.; Pawar, Sampada S.; Gandhi, S. V.
A new sensitive, simple, rapid and precise method for simultaneous estimation of paracetamol and aceclofenac in combined tablet dosage form has been developed. The method is based on ratio derivative spectrophotometry. The amplitude in first derivative of the ratio spectra at 256 nm and 268 nm (minima) were selected to determine paracetamol and aceclofenac in combined formulation. The method showed good linearity, accuracy and reproducibility. Results of analysis were validated statistically and by recovery studies. PMID:21394261
Metzmann, Katrin; Schnell, David; Jungnik, Arvid; Ring, Arne; Theodor, Rudolf; Hohl, Kathrin; Meinicke, Thomas; Friedrich, Christian
The objectives of the studies reported here were to determine the relative bioavailability of linagliptin and metformin when administered in a fixed-dose combination (FDC) tablet with and without food, and to investigate the relative bioavailability of linagliptin and metformin FDC tablets from two treatment batches with different dissolution behavior. These studies were open-label, single-dose, randomized, two-way crossover trials. After an overnight fast, healthy volunteers received an FDC tablet once (with/without food in the food-effect study; or from one of two batches with differing dissolution behavior in the tablet-dissolution study). On a separate visit, following a washout period of 35 days, participants received the alternative treatment. In the food-effect study the primary endpoints were maximum measured concentration in plasma (C(max)) for linagliptin and metformin, area under the plasma concentration-time curve from 0 to 72 hours (AUC(0-72)) for linagliptin and from 0 to infinity (AUC(0-inf)) for metformin. In the tablet-dissolution study the primary endpoints were Cmax for both analytes, AUC(0-72) for linagliptin, and from 0 to the time of the last quantifiable data point (AUC(0-t)) for metformin. The administration of the FDC tablet with food had no influence on the relative bioavailability of linagliptin and metformin with regard to the extent of exposure as determined by AUC(0-72) (linagliptin) and AUC(0-inf) (metformin) compared with FDC tablet administration while fasting. After food intake, peak plasma concentrations of linagliptin were slightly lowered (from 4.99 to 4.56 nmol L⁻¹), but the 90% confidence interval (CI) of the geometric mean test/reference ratio was still located within the generally applied bioequivalence acceptance limits of 80 - 125%. The median time from dosing to the maximum concentration of linagliptin in plasma (t(max)) was similar under both conditions. Administration with food reduced the rate of absorption of
. This is due to raw materials contamination and unhygienic production conditions. In this study, microbiological quality of some herbal solid dosage forms from public markets, in the city of Sari, Iran was examined. 20 herbal products as tablet, ...
Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Uchida, Takahiro
The purpose of this study was to evaluate the palatabilities of the original and nine generic versions of famotidine orally disintegrating tablets (FODTs) by means of disintegration times and bitterness intensities determined using in combination disintegration device and taste sensor comparison of human gustatory sensation tests. The disintegration times were determined using a new disintegration testing equipment for ODTs, the OD-mate and bitterness intensities were determined using the SA501C taste-sensing system. The disintegration time and bitterness of each FODT was evaluated in gustatory sensation tests. There was a good correlation between the disintegration times of 10 FODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of FODTs at 10, 20 and 30 s after starting the disintegration using the OD-mate and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. A combination of the OD-mate and the SA501C was capable of predicting the palatabilities, disintegration properties and bitterness intensity of FODTs.
Ragab, Marwa A A; El-Kimary, Eman I
A new combination of ibuprofen (NSAID) and famotidine (H2 receptor antagonist) was recently approved by the FDA. It was formulated to relief pain while decreasing the risk of ulceration, which is a common problem for patients receiving NSAID. A rapid and simple derivative emission spectrofluorimetric method is proposed for the simultaneous analysis of this combination in their pharmaceutical preparation. The method is based upon measurement of the native fluorescence intensity of the two drugs at λex = 233 nm in acetonitrile. The emission data were differentiated using the first (D1) derivative technique. The plots of derivative fluorescence intensity versus concentration were rectilinear over a range of 2-35 and 0.4-8 µg/mL for both ibuprofen (IBU) and famotidine (FAM), respectively. The method was sensitive as the limits of detection were 0.51 and 0.12 µg/mL and limits of quantitation were 1.70 and 0.39 µg/mL, for IBU and FAM respectively. The proposed derivative emission spectrofluorimetric method was successfully applied for the determination of the two drugs in their synthetic mixtures and tablets with good accuracy and precision. The proposed method was validated as per ICH guidelines. Copyright © 2014 John Wiley & Sons, Ltd.
Ciavarella, Anthony B; Khan, Mansoor A; Gupta, Abhay; Faustino, Patrick J
This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units , which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. Tablet splitting has become a very common practice in the United States and throughout the
Chuang, Wan-Long; Chien, Rong-Nan; Peng, Cheng-Yuan; Chang, Ting-Tsung; Lo, Gin-Ho; Sheen, I-Shyan; Wang, Horng-Yuan; Chen, Jyh-Jou; Yang, Jenny C; Knox, Steven J; Gao, Bing; Garrison, Kimberly L; Mo, Hongmei; Pang, Phillip S; Hsu, Yu-Chun; Hu, Tsung-Hui; Chu, Chi-Jen; Kao, Jia-Horng
Pegylated-interferon-alpha plus ribavirin is the current standard-of-care regimen for treating chronic hepatitis C virus (HCV) infection in Taiwan; however, interferon-based regimens can be poorly tolerated. The interferon-free, two-drug, fixed-dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the USA, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients. In this multicenter, open-label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n = 42, treatment-naïve; n = 43, treatment-experienced) with chronic genotype 1 HCV infection (±compensated cirrhosis) received 12 weeks of ledipasvir/sofosbuvir fixed-dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected. The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment-naïve and treatment-experienced patients, respectively, achieving SVR12. There were no on-treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment-emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3-4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir. Data from this phase 3b study suggest that 12 weeks of once-daily treatment with the interferon-free, ribavirin-free regimen ledipasvir/sofosbuvir is effective and well-tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons
Yang, Yong-Ge; Song, Li-Xue; Jiang, Nan; Xu, Xue-Ting; Di, Xiao-Hui; Zhang, Mei
Objective: To investigate the pharmacokinetics of Ambroxol and Clenbuterol Tablets in Chinese healthy volunteers after a single or multiple dosages oral administration. Methods: A total of 9 healthy adult subjects were given Ambroxol and Clenbuterol Tablets in a single dosage or multiple dosages respectively. LC/MS/MS were used for the determination of Ambroxol and Clenbuterol of in plasma. The important pharmacokinetic parameters were calculated by DAS 2.0 software (compartment model). Resul...
Liu, Xiaohong; Wang, Shang; Chai, Liqing; Zhang, Dong; Sun, Yinghua; Xu, Lu; Sun, Jin
In order to decrease the fluctuation of blood concentration and to increase the oral bioavailability of nimodipine (NMD), a two-step strategy including the push-pull osmotic pump (PPOP) method in combination with micronization and solid dispersion techniques, was used to prepare the controlled-release high-bioavailability solid dosages. The optimization of formulation and process was conducted by comparing effects of different solubilization methods on release behavior of NMD. The in vitro dissolution studies indicated that both the two strategies were able to deliver NMD in the predetermined zero-order manner from 2 to 12h, regardless of effects of release media and agitation rates. Although the Cmax values of two PPOP tablets were lower than that of the reference formulation, both the Tmax values were prolonged, demonstrating the prominent controlled release performance. In comparison with the commercial reference tables, the relative bioavailability of the two formulations was 67.0% and 121.1%, respectively, indicating the solid dispersion technique was more efficient than the micronization technique in terms of solubilization capability and absorption enhancement. In summary, the two-step strategy, combining the push-pull osmotic pump method with the solid dispersion technique, is a very effective method to prepare high bioavailable controlled-release formulations of the poorly soluble drugs, i.e. NMD, taking into account the therapeutical efficiency and safety. Copyright © 2013 Elsevier B.V. All rights reserved.
Savaşer, Ayhan; Taş, Çetin; Bayrak, Ziya; Özkan, Cansel Köse; Özkan, Yalçın
Metoclopramide HCl (MTC) is commonly used for the management of gastrointestinal disorders. It has a short biological half-life and is usually administered four times daily to maintain effective concentrations throughout the day. The aim of this study is to develop sustained-release hydrophilic matrix tablet formulations of drug to achieve reproducible and predictable release rates, extended duration of activity, decreased toxicity, reduction of required dose, optimized therapy, and improved patient compliance. Hydroxypropylmethyl cellulose (HPMC), carboxymethylcellulose sodium (NaCMC), chitosan and Carbopol 981 were incorporated in the matrix system separately or in combinations as release controlling factor by direct compression technique. Compatibility among the formulation components was assessed by DSC and FTIR analysis. MTC release from matrix was evaluated by using the US Pharmacopeia dissolution apparatus II. All formulations met the criteria of pharmacopeial requirements. Dissolution studies show that polymer type and concentration are important parameters on drug release. Chitosan, carbopol and NaCMC formulations exhibited pH-dependent drug release profile whereas HPMC did not. All the formulations containing 1:1 ratio of HPMC and chitosan exhibited desired drug release showing that all active substance releases progressively in a period of whole dissolution time and therefore it can be regarded as worthy of consideration for the manufacture of sustained-release MTC product.
Ellis, J.C.; L'homme, R.F.A.; Ewings, F.M.; Mulenga, V.; Bell, F.; Chileshe, R.; Molyneux, E.; Abernethy, J.; Oosterhout, J.J. van; Chintu, C.; Walker, A.S.; Gibb, D.M.; Burger, D.M.
OBJECTIVE: To investigate nevirapine concentrations in African HIV-infected children receiving divided Triomune tablets (stavudine+lamivudine+nevirapine). DESIGN: Cross-sectional study. METHODS: Steady-state plasma nevirapine concentrations were determined in Malawian and Zambian children aged 8
Genina, Natalja; Boetker, Johan Peter; Colombo, Stefano; Harmankaya, Necati; Rantanen, Jukka; Bohr, Adam
The design and production of an oral dual-compartmental dosage unit (dcDU) was examined in vitro and in vivo with the purpose of physically isolating and modulating the release profile of an anti-tuberculosis drug combination. Rifampicin (RIF) and isoniazid (ISO) are first line combination drugs for treatment of tuberculosis (TB) that negatively interact with each other upon simultaneous release in acidic environment. The dcDUs were designed in silico by computer aided design (CAD) and fabricated in two steps; first three-dimensional (3D) printing of the outer structure, followed by hot-melt extrusion (HME) of the drug-containing filaments. The structure of the fabricated dcDUs was visualized by scanning electron microscopy (SEM). The 3D printed compartmentalized shells were loaded with filaments containing active pharmaceutical ingredient (API) and selectively sealed to modulate drug dissolution. The drug release profile of the dcDUs was characterized by pH-transfer dissolution in vitro and pharmacokinetics studies in rats, and resulted in modified release of the APIs from the dcDUs as compared to the free filaments. Furthermore, the selective physical sealing of the compartments resulted in an effective retardation of the in vitro API release. The findings of this study support the development of controllable-by-design dcDU systems for combination therapies to enable efficient therapeutic translation of oral dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.
Lim, P C; Lim, S L; Oiyammaal, C
Type-2 diabetes mellitus (T2DM) patients who were on gliclazide co-administered with metformin were changed to pre-combined glibenclamide-metformin tablets in the Endocrine Clinic, Penang Hospital. We conducted a retrospective study to evaluate the differences in glycaemic control and treatment cost following the change. Eighty patients (60% females) with a mean age of 55 years old were studied. Mean glycosylated haemoglobin (HbAlc) reduction was -0.92% (p or =8% had greater reduction in mean HbA1c (-1.36%) after six months. The treatment cost per month was reduced by 45% at 3 months (pchange to pre-combined glibenclamide-metformin tablets resulted in significant improvement in glycaemia and reduction in treatment cost
Siahi-Shadbad, Mohammad R; Asare-Addo, Kofi; Azizian, Kakali; Hassanzadeh, Davoud; Nokhodchi, Ali
The objective of this study was to investigate the release behaviour of propranolol hydrochloride from psyllium matrices in the presence hydrophilic polymers. The dissolution test was carried out at pH 1.2 and pH 6.8. Binary mixtures of psyllium and hydroxypropyl methylcellulose (HPMC) used showed that an increase in the percentage of HPMC in the binary mixtures caused a significant decrease in the release rate of propranolol. Psyllium-alginate matrices produced lower drug release as compared to when the alginate was the matrix former alone. When sodium carboxy methyl cellulose (NaCMC) was incorporated into the psyllium, the results showed that matrices containing the ratio of psyllium-NaCMC in the 1:1 ratio are able to slow down the drug release significantly as compared to matrices made from only psyllium or NaCMC as retardant agent suggesting that there could be a synergistic effect between psyllium and NaCMC. The double-layered tablets showed that the psyllium and HPMC in the outer shell of an inner formulation of psyllium alone had the greatest effect of protecting the inner core and thus producing the lowest drug release (DE = 38%, MDT = 93 min). A significant decrease in the value of n in Q = kt(n) from 0.70 to 0.51 as the psyllium content was increased from 50 to 150 mg suggests that the presence of psyllium in HPMC matrices affected the release mechanism. Psyllium powder had the ability in the combination with other hydrophilic polymers to produce controlled release profiles. Care and consideration should as such be taken when formulating hydrophilic matrices in different combinations.
Pharmacokinetics of metronidazole, tetracycline and bismuth in healthy volunteers after oral administration of compound tablets containing a combination of metronidazole, tetracycline hydrochloride and bismuth oxide.
Wu, Y; Ding, L; Huang, N-Y; Wen, A-D; Liu, B; Li, W-B
To eradicate Helicobacter pylori in human pylorus and to heal duodenal ulcers, recently, a new formulation of combination tablets containing metronidazole 125 mg, tetracycline hydrochloride 125 mg and bismuth oxide 40 mg has been developed. To investigate the pharmacokinetics of metronidazole, tetracycline and bismuth in healthy Chinese volunteers after oral administration of the test formulation. A one-sequence, 3-period study was conducted in 12 Chinese healthy volunteers (6 male, 6 female). Volunteers each received single low dose (1 tablet) under fed condition in period 1, single high dose (3 tablets) under fasted condition in period 2, and single high dose (3 tablets) and multiple doses (3 tablets at once, 4 times daily for 7 consecutive days) under fed condition in period 3. Blood samples were collected and determined over 48 h in every period. After single high dose administration under fed condition, the C max of metronidazole, tetracycline and bismuth were 6.833 ± 0.742 μg/mL, 0.8513 ± 0.1253 μg/mL and 3.32 ± 1.89 ng/mL, respectively. The C max and AUC 0-48 of metronidazole increased in proportion to the doses within the tested dose range, but tetracycline and bismuth did not. Food caused 10% and 80% decrease of the C max for metronidazole and bismuth, respectively, but did not affect tetracycline. No gender effect was found on the pharmacokinetics of the 3 ingredients. In the steady state, the C av of metronidazole, tetracycline and bismuth were 20.75 ± 3.52 μg/mL, 1.900 ± 0.243 μg/mL and 5.61 ± 1.34 ng/mL, respectively. © Georg Thieme Verlag KG Stuttgart · New York.
Olsson, H; Nyström, C
The aim of this article was to study the possibility of assessing the structural features affecting tablet tensile strength to obtain information on the dominating bond types, i.e. interparticulate attractions, in tablets. The features of the internal tablet structure considered to be important for tablet tensile strength were assessed using a simple tablet model for tablets made from seven materials: potassium chloride, sodium chloride, sodium bicarbonate, lactose, sucrose, microcrystalline cellulose, and ascorbic acid. Tablet porosity and particle size (measured as external specific surface area by permeametry) were the structural features that best correlated with tablet tensile strength. These features were described by a "structural factor," which was combined with tablet tensile strength, as an "interaction factor," to reflect the dominating bond types in tablets. The qualitative results gave dominating bond types in the tablets studied that matched the results of earlier studies, thus supporting the applicability of the method.
Charlton, R E; Cardé, R T
The relative efficacy of disruptant blends comprised of different combinations of the Oriental fruit moth's pheromone components was determined in field tests. Disruption was evaluated by comparing male moth catch at synthetic and female-baited traps in disruptant and non-treatment areas. Three atmospheric dosages of a 8-dodecenyl acetate (93.5%Z∶6.5%E) blend, representing two successive 10-fold decreases in concentration (2.5 × 10(-2) g/hectare/day to 2.5 × 10(-4) g/hectare/day) were tested alone and in combination with an additional percentage of (Z)-8-dodecen-1-ol. Male moth orientation to traps was eliminated in plots exposed to the two highest binary acetate dosages. However, significantly more males were captured in synthetic-baited traps in the lowest acetate-alone treatment, indicating a diminution of disruption efficiency. In contrast, inclusion of (Z)-8-dodecen-1-ol in the disruptant blend effected essentially complete disruption of orientation at all concentrations tested. Mating success ofG. molesta pairs confined in small cages apparently was not affected by the presence of relatively high concentrations of the binary acetate and the acetate-alcohol blends. This suggests that habituation and/or adaptation of male response, at least for comparatively "close-range" behaviors, did not occur.
Sagar Suman Panda
Full Text Available A novel, simple, accurate and precise RP-HPLC method for simultaneous determination of levosalbutamol sulfate and theophylline has been developed and validated. Separation was achieved on a Phenomenex; C18 column (250 mm × 4.6 mm i.d., 5 µm using methanol: 10 mM TBAHS(tetrabutyl ammonium hydrogen sulfate (50:50, v/v as mobile phase at flow rate of 1.0 mL.min-1. The UV detection wavelength was 274 nm. The linearity is obeyed over a concentration range of 0.5-150 µg.mL-1 with correlation coefficient of 0.999 for both the drugs. The proposed method was validated by determining accuracy, precision, stability and system suitability parameters. The method was found to be robust. Specificity of the method was determined by subjecting the drugs to various stress conditions like acid, alkali, oxidation, thermal and photolytic degradation. The method was used successfully for the simultaneous determination of levosalbutamol sulfate and theophylline in syrup dosage form.
Duggan, Joan M; Akpanudo, Barbara; Shukla, Vipul; Gutterson, Glen; Eitniear, Lindsey; Sahloff, Eric G
Evidence-based guidance is presented to assist clinicians in selecting alternative formulations of antiretroviral (ARV) agents for patients with human immunodeficiency virus (HIV) infection who are unable to swallow tablets or capsules. The inability to take medications in standard oral dosage forms can be associated with nonadherence or the use of alternative administration strategies such as capsule or tablet breaking, crushing, or chewing. Patients with HIV infection require long-term ARV therapy to maintain viral suppression; ARV agents are predominately available as tablets and capsules that may pose swallowing difficulties for some patients. Using a variety of sources (the primary literature, pharmaceutical package inserts, and requests for unpublished data from drug manufacturers), available evidence on the bioavailability of ARV medications after disruption of the capsule or tablet matrix was reviewed; information on alternative formulations of ARV agents was also assessed. With several ARV agents, disruption of the solid oral dosage form by crushing, chewing, or breaking tablets or opening capsules prior to ingestion has been shown to result in altered bioavailability or pharmacokinetics and thus the potential for incomplete virological suppression, increased adverse effects, and suboptimal health outcomes. Of the 33 single-agent ARV medications and combination ARV products in five classes available at the time of review, approximately half exist as powders, liquids, injectables, or chewable or dissolvable tablets. If alternative ARV formulations or administration methods are used, close monitoring for achievement of virological and immunologic success and potential toxicities is recommended. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.
Formulation design of double-layer in the outer shell of dry-coated tablet to modulate lag time and time-controlled dissolution function: Studies on micronized ethylcellulose for dosage form design (VII)
Lin, Shan-Yang; Lin, Kung-Hsu; Li, Mei-Jane
The dry-coated tablet with optimal lag time was designed to simulate the dosing time of drug administration according to the physiological needs. Different compositions of ethylcellulose (EC) powder with a coarse particle (167.5 μm) and several fine particles (
German, Polina; Mathias, Anita; Brainard, Diana; Kearney, Brian P
Ledipasvir/sofosbuvir (Harvoni ® ), a fixed-dose combination tablet of an NS5A inhibitor ledipasvir and an NS5B polymerase inhibitor sofosbuvir, is approved in the US, European Union, Canada, and other regions for the treatment of chronic hepatitis C virus infection in adults. Following absorption, ledipasvir reaches maximum plasma concentrations (T max ) 4-4.5 h post-dose and is eliminated with a terminal half-life (t 1/2 ) of 47 h. Sofosbuvir undergoes intracellular activation to an active triphosphate GS-461203 (not detected in plasma) and ultimately to GS-331007, a predominant circulating metabolite, which is the primary analyte of interest in clinical pharmacology studies. Sofosbuvir is rapidly absorbed and eliminated from plasma (T max : 0.8-1 h; t 1/2 : 0.5 h). The peak plasma concentrations for GS-331007 are achieved between 3.5 and 4 h post-dose; the elimination t 1/2 for GS-331007 is 27 h. Ledipasvir/sofosbuvir exhibits a favorable clinical pharmacology profile; it can be administered once daily without regard to food and does not require dose modification in hepatitis C virus-infected patients with any degree of hepatic impairment or mild to moderate renal impairment. The pharmacokinetic profiles of ledipasvir, sofosbuvir, and GS-331007 (predominant circulating metabolite of sofosbuvir) are not significantly affected by demographic variables; pharmacokinetic/pharmacodynamic analyses reveal no exposure-response relationships for efficacy or safety. The review summarizes the clinical pharmacokinetics, pharmacodynamics, and pharmacokinetic/pharmacodynamic analyses for ledipasvir/sofosbuvir.
Dou, Ying; Sun, Ying; Ren, Yuqiu; Ju, Ping; Ren, Yulin
The two components (paracetamol and amantadine hydrochloride) were simultaneously determined in combined paracetamol and amantadine hydrochloride tablets and powder by using near-infrared (NIR) spectroscopy and artificial neural networks (ANNs). The ANN models of three pretreated spectra (first-derivative, second-derivative and standard normal variate (SNV), respectively) were established. The mathematical corrected models of tablets were compared with those of the powder. In the models, the concentrations of paracetamol and amantadine hydrochloride as the active components were determined simultaneously and compared with the results of their separate determination. The parameters that affected the network were studied and the concentrations of the test set samples were predicted. The degree of approximation, a new evaluation criterion of the network was employed to prove the accuracy of the predicted results.
Full Text Available A rapid and precise method (in accordance with ICH guidelines is developed for the quantitative simultaneous determination of Drotaverine hydrochloride and Omeprazole in a combined pharmaceutical dosage form. Three methods are described for the simultaneous determination of Drotaverine hydrochloride and Omeprazole in a binary mixture. The first method was based on UV-Spectrophotometric determination of two drugs, using Vierordt!s simultaneous equation method. It involves absorbance measurement at 226.8 nm (λmax of Drotaverine hydrochloride and 269.4 nm (λmax of Omeprazole in methanol; linearity was obtained in the range of 5–30 μg ml−1 for both the drugs. The second method was based on HPLC separation of the two drugs using potassium dihydrogen phosphate buffer pH 5.0: Acetonitrile: Triethylamine (60:40:0.5, v/v as a mobile phase. Areas were recorded at 260 nm for both the drugs and retention time was found to be 2.71 min. and 3.87 min for Drotaverine hydrochloride and Omeprazole, respectively at 1.0 mL/min flow rate. The selected chromatographic conditions were found to determine Drotaverine hydrochloride and Omeprazole quantitatively in a combined dosage form without any physical separation. The method has been validated for linearity, accuracy and precision. Linearity was found over the range of 5–30 μg mL−1 for both drugs. The third method was based on HPTLC method for simultaneous quantification of these compounds in pharmaceutical dosage forms. Precoated silica gel 60 F254 plate was used as stationary phase. The separation was carried out using Glacial acetic acid:Cyclohexane:Methanol:(80:15:5 v/v/v as mobile phase. The proposed method was found to be fast, accurate, precise, reproducible and rugged and can be used for a simultaneous analysis of these drugs in combined formulations.
Formulation design of double-layer in the outer shell of dry-coated tablet to modulate lag time and time-controlled dissolution function: studies on micronized ethylcellulose for dosage form design (VII).
Lin, Shan-Yang; Lin, Kung-Hsu; Li, Mei-Jane
The dry-coated tablet with optimal lag time was designed to simulate the dosing time of drug administration according to the physiological needs. Different compositions of ethylcellulose (EC) powder with a coarse particle (167.5 microm) and several fine particles (coated tablets. The formulations containing different weight ratios of coarse/fine particles of EC powders or 167.5 microm EC powder/excipient in the upper layer of the outer shell to influence the release behavior of sodium diclofenac from dry-coated tablet were also explored. The results indicate that sodium diclofenac released from all the dry-coated tablets exhibited an initial lag period, followed by a stage of rapid drug release. When the mixture of the coarse/fine particles of EC powders was incorporated into the whole layer, the lag time was almost the same. The outer shell broke into 2 halves to make a rapid drug release after the lag time, which belonged to the time-controlled disruption of release mechanism. When the lower layer in the outer shell was composed of 167.5 microm EC powder and the upper layer was formulated by mixing different weight ratios of 167.5 microm and 6 microm of EC powders, the drug release also exhibited a time-controlled disruption behavior. Its lag time might be freely modulated, depending on the amount of 6 microm EC powder added. Once different excipients were respectively incorporated into the upper layer of the outer shell, different release mechanisms were observed as follows: time-controlled explosion for Explotab, disruption for Avicel and spray-dried lactose, erosion for dibasic calcium phosphate anhydrate, and sigmoidal profile for hydroxypropyl methylcellulose.
Mahmoud, Enas A; Bendas, Ehab R; Mohamed, Magdy I
The purpose of this study was to combine the advantages of self-nanoemulsifying drug delivery systems and tablets as a conventional dosage form emphasizing the excipients' effect on the development of a new dosage form. Systems composed of HCO-40, Transcutol HP, and medium-chain triglyceride were prepared. Essential properties of the prepared systems regarding carvedilol solubility, a model drug, and self-emulsification time were determined. In order to optimize self-nanoemulsifying drug delivery systems (SNEDDS), formulation dispersion-drug precipitation test was performed in the absence and presence of cellulosic polymers. Furthermore, SNEDDS was loaded onto liquisolid powders. P-glycoprotein (P-gp) activity of the selected SNEDDS was tested using HCT-116 cells. Carvedilol showed acceptable solubility in the selected excipients. It also demonstrated improvement in the stability upon dilution with aqueous media in the presence of cellulosic polymers. Use of granulated silicon dioxide improved the physical properties of liquisolid powders containing SNEDDS. It improved the compressibility of the selected powders and the tested SNEDDS showed marked P-gp inhibition activity. Prepared self-nanoemulsifying tablet produced acceptable properties of immediate-release dosage forms and expected to increase the bioavailability of carvedilol.
Liao, Lin; Yang, Ming; Qiu, Lu-Lu; Mou, Ya-Ru; Zhao, Jia-Jun; Dong, Jian-Jun
Few studies have given suggestions on appropriate initiation insulin dosage when combined with oral antidiabetic drugs (OADs). This research was to investigate appropriate initiation insulin doses for insulin-naive type 2 diabetes patients with different combinations and the relationship between insulin dosage and relevant factors. This was a randomized, open-label, treat to target study. The target was 20% decrease of both fasting plasma glucose (FPG) and 2 hours post-breakfast blood glucose (P2hBG). One hundred and forty-seven insulin-naive Chinese patients recruited were randomly assigned to 3 groups: group A, patients received insulin monotherapy; group B, received insulin plus metformin (0.5 g, tid) and group C, received insulin plus metformin (0.5 g, tid) and pioglitazone (15 mg, qd). Insulin doses were initiated with a dose of 0.3 U×kg(-1)×d(-1) and titrated according to FPG and P2hBG till reached the targets. Both the time of getting 20% reduction of FPG and P2hBG showed significant differences among the three groups. The time was shortest in Group C. The insulin doses needed to achieve glucose reduction of 20% in three treatment groups were (0.40 ± 0.04) U×kg(-1)×d(-1) for Group A, (0.37 ± 0.04) U×kg(-1)×d(-1) for Group B, and (0.35 ± 0.03) U×kg(-1)×d(-1) for Group C, respectively. Multiple linear stepwise regression analysis showed that insulin doses correlated with body weight, FPG, diabetes duration, age and history of sulfonylurea treatment. The standardized regression coefficients were 0.871, 0.322, 0.089, 0.067 and 0.063 (with all P metformin treatment, and 0.35 U×kg(-1)×d(-1) for insulin plus metformin and pioglitazone treatment in Chinese type 2 diabetes outpatients. Body weight is found the most closely related factor to the insulin dosage.
El-Say Khalid M.
Full Text Available This study was aimed at developing risperidone oral disintegrating mini-tablets (OD-mini-tablets as age-appropriate formulations and to assess their suitability for infants and pediatric use. An experimental Box-Behnken design was applied to assure high quality of the OD-mini-tablets and reduce product variability. The design was employed to understand the influence of the critical excipient combinations on the production of OD-mini-tablets and thus guarantee the feasibility of obtaining products with dosage form uniformity. The variables selected were mannitol percent in Avicel (X1, swelling pressure of the superdisintegrant (X2, and the surface area of Aerosil as a glidant (X3. Risperidone-excipient compatibilities were investigated using FTIR and the spectra did not display any interaction. Fifteen formulations were prepared and evaluated for preand post-compression characteristics. The prepared ODmini- tablet batches were also assessed for disintegration in simulated salivary fluid (SSF, pH 6.2 and in reconstituted skimmed milk. The optimized formula fulfilled the requirements for crushing strength of 5 kN with minimal friability, disintegration times of 8.4 and 53.7 s in SSF and skimmed milk, respectively. This study therefore proposes the risperidone OD-mini-tablet formula having robust mechanical properties, uniform and precise dosing of medication with short disintegration time suitable for pediatric use.
Belal, Tarek S; Haggag, Rim S
The pharmaceutical combination of miconazole nitrate (MZ) and lidocaine hydrochloride (LD) is used in the curative and prophylactic therapy of the oral and gastro-intestinal infections caused by Candida albicans. To the best of our knowledge, no attempts have yet been made to assay this combination by any analytical method. A simple and selective high-performance liquid chromatography-diode array detection (HPLC-DAD) stability-indicating method was developed for the simultaneous determination of MZ and LD in their combined formulation. Effective chromatographic separation was achieved using a Zorbax SB-C8 column with gradient elution of the mobile phase composed of 0.05 M phosphoric acid and acetonitrile. The gradient elution started with 25% (by volume) acetonitrile, ramped up linearly to 65% in 6 min, then kept constant until the end of the run. The mobile phase was pumped at a flow rate of 1 mL/min. The multiple wavelength detector was set at 215 nm and analytes were quantified by measuring their peak areas. The retention times for LD and MZ were approximately 4.1 and 8.4 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness, detection and quantification limits. Calibration curves were linear in the ranges of 5-100 µg/ml for both drugs with correlation coefficients > 0.999. Both drugs were subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The proposed method proved to be stability-indicating by the resolution of the two analytes from the related substance and potential impurity (2,6-dimethylaniline) and from the forced-degradation products. The validated HPLC method was applied to the analysis of MZ and LD in the combined oral gel preparation, in which the two analytes were successfully quantified and resolved from the pharmaceutical additives. The proposed method made use
Okwuosa, Tochukwu C; Stefaniak, Dominika; Arafat, Basel; Isreb, Abdullah; Wan, Ka-Wai; Alhnan, Mohamed A
The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing. Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a caplet-shaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of the drugs and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In vitro drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus. Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication of immediate release tablets at temperatures as low as 110°C. The integrity of two model drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate in vitro release pattern. Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.
Radwan, Asma; Zaid, Abdel Naser; Jaradat, Nidal; Odeh, Yousef
The clinical implications of food-drug interactions may have to be taken seriously into account with oral drugs administration in order to minimize variations in drug bioavailability. Food intake may alter physiological changes in the pH and viscosity of the gastrointestinal lumen, which could affect the oral absorption of drugs. The aim of the present study was to have an insight on the effect of media parameters: viscosity and pHon the oral absorption of ciprofloxacin HCl from solid formulations using a model food: Corchorus olitorius (Jute) Soup. In vitro disintegration and dissolution rates of ciprofloxacin tablet were evaluated using compendia buffer media in the presence/absence of C. olitorius leaves. These in vitro data were then input to GastroPlus™ to predict ciprofloxacin absorption profiles under fasted and fed states. The present study demonstrated the significance of luminal pH and viscosity on the dissolution and disintegration of solid formulations following postprandial ingestion of the viscous soup. The tablets showed prolonged disintegration times and reduced dissolution rates in this soup, which could be attributed to the postprandial elevation in media viscosity and reduced solubility at elevated gastricpH. The predicted model under fed state showed no impact on AUC but prolonged Tmax and a decrease in Cmax. Concomitant intake of C. olitorius soup with ciprofloxacin might have negative effect on the rate of drug release from conventional immediate release tablets. Copyright © 2017 Elsevier B.V. All rights reserved.
El-Zaher, Asmaa A.; Elkady, Ehab F.; Elwy, Hanan M.; Saleh, Mahmoud Abo El Makarim
In the present work, pioglitazone and glimepiride, 2 widely used antidiabetics, were simultaneously determined by a chemometric-assisted UV-spectrophotometric method which was applied to a binary synthetic mixture and a pharmaceutical preparation containing both drugs. Three chemometric techniques - Concentration residual augmented classical least-squares (CRACLS), principal component regression (PCR), and partial least-squares (PLS) were implemented by using the synthetic mixtures containing the two drugs in acetonitrile. The absorbance data matrix corresponding to the concentration data matrix was obtained by the measurements of absorbencies in the range between 215 and 235 nm in the intervals with Δλ = 0.4 nm in their zero-order spectra. Then, calibration or regression was obtained by using the absorbance data matrix and concentration data matrix for the prediction of the unknown concentrations of pioglitazone and glimepiride in their mixtures. The described techniques have been validated by analyzing synthetic mixtures containing the two drugs showing good mean recovery values lying between 98 and 100%. In addition, accuracy and precision of the three methods have been assured by recovery values lying between 98 and 102% and R.S.D. % ˂0.6 for intra-day precision and ˂1.2 for inter-day precision. The proposed chemometric techniques were successfully applied to a pharmaceutical preparation containing a combination of pioglitazone and glimepiride in the ratio of 30: 4, showing good recovery values. Finally, statistical analysis was carried out to add a value to the verification of the proposed methods. It was carried out by an intrinsic comparison between the 3 chemometric techniques and by comparing values of present methods with those obtained by implementing reference pharmacopeial methods for each of pioglitazone and glimepiride.
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Milbemycin oxime tablets. 520.1445 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1445 Milbemycin oxime... milbemycin oxime. (2) Cats. Each tablet contains 5.75, 11.5, or 23.0 milligrams of milbemycin oxime. (b...
Efficacy and safety of the losartan-hydrochlorothiazide combination tablet in patients with hypertension uncontrolled by angiotensin II receptor antagonist therapy: the Aichi Research on Combination therapy for Hypertension (ARCH) Study.
Maeda, Kengo; Adachi, Masayoshi; Kinoshita, Atsushi; Koh, Naoki; Miura, Yoshitaka; Murohara, Toyoaki
The guidelines recommend combination therapy for patients who are unable to achieve target BP with monotherapy; some fixed dose therapies including an angiotensin II receptor blocker (ARB) and diuretics are available in Japan. However, to date there have been few reports on this long-term treatment and the patient profiles suited for this combination remain ambiguous. The Aichi Research on Combination therapy for Hypertension Study was a multicenter, open-label, prospective observational study that investigated the efficacy and safety of 1-year treatment with the losartan-hydrochlorothiazide (HCTZ) combination tablet in patients with hypertension uncontrolled by either ARB monotherapy or combination therapy with a calcium channel blocker (CCB). An ARB was switched to a losartan-HCTZ tablet after a pre-observation period. A total of 614 of 648 patients were evaluable (mean age, 66.3 years; 52.8% men; mean baseline blood pressure, BP, 157.7/87.9 mmHg). The BP had decreased significantly to 138.0/78.2 mmHg by month 3 (p<0.001, t-test), and 36.2% of the patients had achieved their target BP. The hypotensive effect lasted for 1 year and was found equally in the losartan-HCTZ arm and the losartan-HCTZ plus CCB arm. A stratified analysis showed significant hypotensive effects in patients with higher baseline BP, women, and patients who did not drink alcohol (p<0.001, unpaired t-test). The losartan-HCTZ combination tablet was found to have an early hypotensive effect, good tolerability, and stable long-term benefits in patients with hypertension uncontrolled by ARB monotherapy or combination therapy with a CCB.
Joshi, Anjali; Gbadero, Daniel; Esseku, Fredrick; Adesanya, Olufikayo J; Adeyeye, Moji C
The bioequivalence study was conducted to compare the developed paediatric fixed-dose combination (FDC) zidovudine/lamivudine/nevirapine (60/30/50 mg) tablet - the test formulation - with the combined mixture of single-entity innovator products (reference product). A single-dose open-label randomized two-way crossover study was conducted in healthy adult African volunteers after an informed consent was obtained. The 24 volunteers, divided into two groups, were administered the products after an overnight fast on two treatment days with 14 days of washout period. Blood samples were collected for 96 h and analysed using a validated RP-HPLC-UV assay method. Pharmacokinetic (PK) parameters (non-compartmental model) were assessed with WinNonlin® software. Analysis of variance (ANOVA) and FDA bioequivalence statistical criterion of 90% CI or 80% to 125% range (set at P 0.05). The 90% CIs for all the drugs were within the 80% to 125% range. The developed FDC tablet is bioequivalent to the reference product. © 2016 Royal Pharmaceutical Society.
Valizadeh, Sousan; Rasekhi, Mehri; Hamishehkar, Hamed; Asadollahi, Malihe; Hamishehkar, Hadi
Considering the inability of neonates to swallow oral drugs in the form of solid tablets, the lack of appropriate dosage forms for infants, and the necessity to prepare some pills for neonates, the current study investigated dosage accuracy in drugs for neonates prepared from tablets by analyzing the concentrations of final products. Captopril and spironolactone, oral dosage forms that are not suitable for infants, were chosen as the drug model for this study. Demographic characteristics of nurses providing medications and tablet preparation methods were documented in a random observational method. To determine concentrations of final solutions, 120 drug samples (60 captopril and 60 spironolactone samples) prepared by Neonatal Intensive Care Unit nurses of the Children Cure and Health Hospital of Tabriz University of Medical Sciences were analyzed using high performance liquid chromatography (HPLC) and spectrophotometry. There was a significant error rate in the concentration of captopril in prepared solutions compared with the ordered dosage. No differences were observed in the demographic characteristics of the nurses and the method of preparation between the two drugs. The only difference related to the preparation technique was that in most cases (70.8%), one whole spironolactone tablet was used, whereas in around 50% of samples in captopril group, half or a quarter of one captopril tablet was utilized for the intended dosage (P = 0.009). This research suggests that the use of a whole tablet instead of a divided tablet in the manual preparation of medication dosage forms for neonates is the most appropriate approach.
Parikh Vikas C.; Karkhanis V.V
A simple, sensitive and accurate UV spectrophotometric method has been developed for the determination of Gemfibrozil in bulk and pharmaceutical tablet dosage formulation. This method obeys Beer’s law in the concentration range of 30-90 µg/ml. with correlation coefficient of 0.9993 and exhibiting maximum absorption at 276 nm with apparent molar absorptivity of 0.1703 × 104 L mole-1 cm-1. The method is accurate and precise and is extended to pharmaceutical tablet dosage forms and there was no ...
Sharma, Garima; Jain, S; Tiwary, A K; Kaur, Gurpreet
In this study, a bioadhesive dosage form of clotrimazole was designed using a combination of bioadhesive polymers Carbopol 934P, sodium carboxymethyl cellulose and sodium alginate in different ratios. The bioadhesive strength was evaluated by measuring the force required to detach the tablets from porcine vaginal mucosal membrane. The strong interaction between polymer and mucus lining of the tissue helps increase the contact time and permits localization of activity. Carbopol 934P showed maximum bioadhesion and required maximum force for detachment; the force required for detachment was directly proportional to its content. The formulations were tested for their swelling behavior using the agar gel plate method. The swelling index was a function of the concentration of the hydrophilic polymer and the formulations containing Carbopol 934P and sodium carboxymethyl cellulose were found to swell to a greater extent than those containing Carbopol and sodium alginate. In vitro release studies showed that the batch consisting of 2:1 ratio of Carbopol 934P/sodium alginate (batch C3) released clotrimazole over 24 h. The similarity factor showed that the dissolution profiles of fresh and aged tablets were similar, suggesting good stability of vaginal tablets prepared using a combination of Carbopol 934P and sodium alginate.
Full Text Available A dissolution method with robust high performance liquid chromatographic (HPLC analysis for immediate release tablet formulation was developed and validated to meet the requirement as per International Conference on Harmonization (ICH and United States Food and Drug Administration (USFDA guidelines. The method involved the use of Agilent ZORBAX Eclipse XDB C18 column, and temperature was maintained at 30Â Â°C. After optimization, the mobile phase was selected as phosphate buffer (KH2PO4, 30Â mM : ACN (60:40, v/v with pH 3.0, and retention time Rt was found as 3.24, 4.16, and 2.55Â min for paracetamol (PCM, chlorpheniramine maleate (CPM and phenylephrine hydrochloride (PH respectively at 265Â nm and at a flow rate of 1Â mL/min. The relative standard deviation (%RSD for 6 replicate measurements was found to be less than 2%. Furthermore net analyte signal standard addition method (NASSAM with spectrophotometer was performed for standard and liquid oral suspension. On the basis of selectivity, sensitivity and accuracy analysis, it was confirmed that this novel method could be useful for simultaneous estimation of the given drug combinations. Two-way analysis of variance (ANOVA was applied for evaluating the statistical difference between the assay results obtained via both NASSAM and RPâHPLC methods and ultimately no significant difference was found between both the methods. All the methods and results were acceptable and confirmed that the method was suitable for intended use. Keywords: Dissolution, RPâHPLC, Net analyte signal standard addition method, Two-way ANOVA
Szałek, Edyta; Karbownik, Agnieszka; Murawa, Dawid; Połom, Karol; Urbaniak, Bartosz; Grabowski, Tomasz; Wolc, Anna; Więckiewicz, Aleksandra; Grześkowiak, Edmund; Kokot, Zenon J; Murawa, Paweł; Burchardt, Paweł; Cieśla, Sławomir
Tramadol/paracetamol is a fixed-dose combination prescribed for the relief of moderate to severe pain. The combination acts synergistically and guarantees the rapid onset of paracetamol and the prolonged analgesic effect of tramadol with good tolerability. These drugs are often used in various formulations in the treatment of patients with postoperative pain, e.g. after stomach resection. Gastrectomy leads to pathophysiological changes within the alimentary tract, which may affect the process of drug absorption. The aim of the research was an analysis of the pharmacokinetics of tramadol/paracetamol from effervescent and conventional tablets in patients after total gastrectomy. The research was carried out on patients after gastrectomy with Roux-en-Y reconstruction. The patients received two tramadol/paracetamol fixed-dose combination tablets in a single orally administered dose of 75/650 mg (2 × 37.5/325 mg). The patients were subjected to one of the two study drug group with: I. effervescent tablet (ET) (n = 14; mean [SD] age, 63.4 [10.1] years; weight, 75.5 [15.3]kg; and BMI, 26.0 [4.6]kg/m(2)) and II. conventional tablet (CT) (n = 12; mean [SD] age, 66.8 [7.7] years; weight, 79.8 [17.8]kg; and BMI, 27.4 [5.3]kg/m(2)). Blood samples were collected within 10 h after the drug administration. The plasma concentrations of tramadol and paracetamol were measured with validated HPLC (high-performance liquid chromatography) method with UV detection. The comparison of the paracetamol and tramadol C(max) ratio for the ET group with that of the CT group gave ratios of 1.16 [90% confidence interval (CI) 1.06, 1.27] and 0.86 (90% CI 0.72, 1.02), respectively. The comparison of the paracetamol and tramadol AUC(0-t) ratio for the ET group with that of the CT group showed ratios of 0.99 (90% CI 0.88, 1.10) and 1.00 (90% CI 0.82, 1.22), respectively. The comparison of the difference for the effervescent and conventional formulation gave an estimated decrease in t(max) of 0.5 h
Full Text Available Buccoadhesive drug delivery systems have distinct advantages in comparison with oral administration. Plant exudates like gum or mucilage are being studied for their use as pharmaceutical adjuvant. The aim of this study is to evaluate the properties of the Plantago major seed mucilage as a mucoadhesive agent and propranolol hydrochloride is chosen as a model drug. Mucoadhesive tablets of propranolol hydrochloride were formulated by combination of two mucoadhesive polymers include Carbopol 934P and Plantago major mucilage, and properties such as in vitro drug release, swelling, erosion, mucoadhesive force were studied. The results show increase in bioadhesive strength and decrease in release rate with increase in percent of Carbopol 934P, as F13 (containing Carbopol 934P alone and F8 (containing mucilage alone show the highest bioadhesive strength and highest release rate respectively and these results were matched to swelling results which decrease in swelling of matrices results in decrease in bioadhesion. Matrices with both Plantago major mucilage and Carbopol have the optimum drug release in bioadhesive formulation of propranolol tablets.
... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.960 Flumethasone tablets. (a..., such as arthritis, the disc syndrome, and myositis. (ii) Dogs and cats: It is used in certain acute and... nephritis, cushingoid syndrome, or where peptic ulcers occur, except for emergency therapy. Clinical and...
Full Text Available The selection of a suitable superdisintegrant for a rapidly disintegrating dosage form is of utmost importance, since disintegration time is a critical parameter. An experimental design was designed so as to find out the effect of superdisintegrants (sodium starch glycollate, crospovidone, croscarmellose sodium and Methacrylic copolymer with divinyl benzene at 2, 4, 6% w/w and its effect on hardness with respect to disintegration time. 4% w/w methacrylic copolymer with divinyl benzene is selected as the best superdisintegrant, effective enough for Tramadol. With increase in hardness, there was a considerable increase disintegration time with all concentrations of superdisintegrants. Crospovidone and Methacrylic copolymer with divinyl benzene in combination showed a remarkable drop in disintegration time upto 0.33 min. Stability Studies of the batch with lowest disintegration time was also carried out and suggests that there was no degradation with respect to time. The selection of a suitable superdisintegrant for a rapidly disintegrating dosage form is of the utmost importance, since disintegration time (DT is a critical parameter. An experimental design was implemented, to find out the effects of superdisintegrants (sodium starch glycolate, crospovidone, croscarmellose sodium and methacrylic copolymer with divinyl benzene, at 2, 4, 6% w/w, on tablet hardness, with respect to DT. Methacrylic copolymer with divinyl benzene (at 4 wt% was selected as the best superdisintegrant, adequate for the formulation of dispersible Tramadol tablets. With increasing hardness, there was a considerable increase in DT at all concentrations of superdisintegrants. A combination of crospovidone and methacrylic copolymer with divinyl benzene showed a remarkable drop in DT to 0.33 min. The stability of the batch with lowest DT was also tested under various conditions and the results suggested that there was no degradation over the test period. Keywords: Tramadol
Full Text Available Objective: Treated the patients with acute coronary syndrome by the DanHong injection combined with Clopidogrel hydrogen sulphate tablets, and defined the effect of this combined treatment on the serum inflammatory factors, the level of platelet activation and the vascular endothelium function. Methods: Selected 102 ACS patients who were admitted in our hospital from December 2014 to April 2016 as the research subjects, and divided them into the control group and observation group according to the data sheet method, each group was composed of 51 cases. The control group was treated with conventional therapy and Clopidogrel hydrogen sulphate tablets, the observation was given DanHong injection additionally on the basis of control group. The treatment period was 2 months. Detected the change level of related indexes of all patients before and after treatment, which contained the serum inflammatory factors (IL-6, TNF-α, hs-CRP, the level of platelet activation (sCD40L, CD62p, GPIIb/IIa receptor compound, and the vascular endothelium function (NO, ET-1, and vWF. Results: It was showed that each index of this two groups was no statistical significant (P>0.05 before treatment. After treatment, the level of IL-6, TNF-α, hs-CRP, sCD40L, CD62p, GPIIb/IIa receptor compound, ET-1 and vWF were decreased dramatically compared with that before treatment, it was statistical significant difference (P<0.05; Moreover, these indexes in the observation group was lower than the control group, there was statistical significant difference between this two groups (P<0.05. The NO level of all patients was increased significantly after treatment (P<0.05, and the level in observation group was increased more obviously than the control group, the interlock difference was statistical significant (P<0.05. Conclusions: It was confirmed that the DanHong injection combined with Clopidogrel hydrogen sulphate tablets could ameliorate the level of serum inflammatory factors
Fed and Fasted Single-dose Assessment of Bioequivalence of Dapagliflozin and Metformin Extended-release Fixed-dose Combination Tablets Relative to Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Subjects.
Boulton, David W; Chang, Ming; Griffen, Steven C; Kitaura, Catia; Lubin, Susan; Pollack, Allyson; LaCreta, Frank
In patients with type 2 diabetes mellitus, fixed-dose combinations (FDCs) of antihyperglycemic medications may provide complementary efficacy while reducing tablet burden and improving compliance. The aim of this study was to assess the bioequivalence and tolerability of 2 FDCs of dapagliflozin and metformin extended-release (XR) versus their individual component (IC) tablets. An open-label, balanced, randomized, 2-way crossover, 4-arm study was conducted in 129 healthy Brazilian subjects (aged 18-55 years). Two oral doses of the FDCs (5 mg dapagliflozin and 500 mg metformin XR, and 10 mg dapagliflozin and 1000 mg metformin XR) were evaluated in fed and fasted states. Under fed and fasted conditions the 5 mg dapagliflozin and 500 mg metformin XR FDC showed bioequivalence to its ICs. The 10 mg dapagliflozin and 1000 mg metformin XR FDC was bioequivalent to its ICs in fed subjects. Although AUC for the 10 mg dapagliflozin and 1000 mg metformin XR FDC was bioequivalent in fasted subjects, the Cmax for metformin was not bioequivalent to its ICs in fasted subjects (upper 90% CI was 127.5%, and thus outside the 80%-125% bioequivalence interval). The small increase in the fasted state is not considered clinically meaningful due to the small magnitude of the difference (9.2%), the lack of metformin Cmax being associated with efficacy or tolerability concerns, and the fasted state not being the recommended state for dosing of metformin XR. The safety profile and tolerability of the FDCs were similar to those of their ICs and no deaths or serious adverse events were reported. Both FDCs of dapagliflozin and metformin XR were bioequivalent to their ICs in fed and fasted subjects, except for the metformin Cmax from the 10 mg dapagliflozin and 1000 mg metformin XR FDC in fasted subjects. These data support the use of a dapagliflozin and metformin XR FDC in patients with type 2 diabetes mellitus. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.
Full Text Available Gabriel Rebick, Sharon L WalmsleyDivision of Infectious Diseases, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, CanadaAbstract: Atripla is the first once-daily, single-tablet, triple-combination antiretroviral therapy. It is recommended for the initial treatment of the naïve patient with human immunodeficiency virus-1 (HIV-1 infection in all current guidelines, based on its proven efficacy in numerous head-to-head randomized clinical trials. Not only has it proven efficacy, but the fixed-dose combination, Atripla, has resulted in an improvement in adherence, quality of life, and satisfaction among naïve as well as virally suppressed patients switching from another regimen. Despite the advantages, tolerability issues can arise that are related primarily to the efavirenz component, which is known to cause central nervous side effects such as dizziness, abnormal dreams, and anxiety. Although generally self-limited, these side-effects can lead to treatment discontinuation in the short- or long-term. Based on the observation of neural tube defects in macaque models, and isolated case reports in human fetuses with first trimester exposure, it is rated as Food and Drug Administration pregnancy category D, and considered as contraindicated in the first trimester of pregnancy where alternatives are available. Given the low genetic barrier of each of the individual components, resistance remains an important issue for patients with poor adherence, but is balanced in part by the long half-life of the drugs. Transmitted resistance is described in up to 16% of newly infected patients in population surveys, and is particularly prevalent in men who have sex with men. Minority variants that may impart resistant to efavirenz are not detected with currently used HIV-1 genotype assays, but nonetheless may also be implicated in patients who fail initial treatment. Several single-tablet regimens are recently licensed or in
Klausner, Eytan A; Lavy, Eran; Friedman, Michael; Hoffman, Amnon
Expandable gastroretentive dosage forms (GRDFs) have been designed for the past 3 decades. They were originally created for possible veterinary use, but later the design was modified for enhanced drug therapy in humans. These GRDFs are easily swallowed and reach a significantly larger size in the stomach due to swelling or unfolding processes that prolong their gastric retention time (GRT). After drug release, their dimensions are minimized with subsequent evacuation from the stomach. Gastroretentivity is enhanced by the combination of substantial dimensions with high rigidity of the dosage form to withstand the peristalsis and mechanical contractility of the stomach. Positive results were obtained in preclinical and clinical studies evaluating GRT of expandable GRDFs. Narrow absorption window drugs compounded in such systems have improved in vivo absorption properties. These findings are an important step towards the implementation of expandable GRDFs in the clinical setting. The current review deals with expandable GRDFs reported in articles and patents, and describes the physiological basis of their design. Using the dog as a preclinical screening model prior to human studies, relevant imaging techniques and pharmacokinetic-pharmacodynamic aspects of such delivery systems are also discussed.
Chandra Sekhar Patro
Full Text Available Our aim was to employ experimental design to formulate and optimize cetirizine hydrochloride oral disintegrating tablets (ODTs by direct compression technique, using the mutual effect of synthetic croscarmellose sodium (CCS and natural Hibiscus rosa-sinensis mucilage (HRM as disintegrants in the formulation. Central composite design (CCD was applied to optimize the influence of three levels each of CCS (X1 and HRM (X2 concentrations (independent variables for investigated responses: disintegration time (DT (Y1, % friability (F (Y2, and % cumulative drug release (DR (Y3 (dependent variables. This face-centered second-order model’s reliability was verified by the probability and adequate precision values from the analysis of variance, while the significant factor effects influencing the studied responses were identified using multiple linear regression analysis. Perturbation and response surface plots were interpreted to evaluate the responses’ sensitivity towards the variables. During optimization, the concentrations of the processed factors were evaluated, and the resulting values were in good agreement with predicted estimates endorsing the validity. Spectral study by Fourier Transform Infrared Spectroscopy (FTIR and thermograms from Differential Scanning Calorimetry (DSC demonstrated the drug-excipients compatibility of the optimized formulation. The optimized formulation has concentrations of 9.05 mg and 16.04 mg of CCS and HRM each, respectively, and the model predicted DT of 13.271 sec, F of 0.498, and DR of 99.768%.
Patro, Chandra Sekhar; Sahu, Prafulla Kumar
Our aim was to employ experimental design to formulate and optimize cetirizine hydrochloride oral disintegrating tablets (ODTs) by direct compression technique, using the mutual effect of synthetic croscarmellose sodium (CCS) and natural Hibiscus rosa-sinensis mucilage (HRM) as disintegrants in the formulation. Central composite design (CCD) was applied to optimize the influence of three levels each of CCS ( X 1 ) and HRM ( X 2 ) concentrations (independent variables) for investigated responses: disintegration time (DT) ( Y 1 ), % friability ( F ) ( Y 2 ), and % cumulative drug release (DR) ( Y 3 ) (dependent variables). This face-centered second-order model's reliability was verified by the probability and adequate precision values from the analysis of variance, while the significant factor effects influencing the studied responses were identified using multiple linear regression analysis. Perturbation and response surface plots were interpreted to evaluate the responses' sensitivity towards the variables. During optimization, the concentrations of the processed factors were evaluated, and the resulting values were in good agreement with predicted estimates endorsing the validity. Spectral study by Fourier Transform Infrared Spectroscopy (FTIR) and thermograms from Differential Scanning Calorimetry (DSC) demonstrated the drug-excipients compatibility of the optimized formulation. The optimized formulation has concentrations of 9.05 mg and 16.04 mg of CCS and HRM each, respectively, and the model predicted DT of 13.271 sec, F of 0.498, and DR of 99.768%.
A double-blind comparative study of Chinese herbal medicine Jinlianqingre Effervescent Tablets in combination with conventional therapy for the treatment of uncomplicated hand, foot, and mouth disease.
He, L-Y; Zhang, G-L; Yan, S-Y; Liu, Y; Zhao, C-S; Wang, X-L; Li, Y; Mi, Y-Q; Liu, Y-M; Li, C-P; Kou, Y-H; Li, Y; Chang, K; Meng, X-L; Sun, X-J; Zhao, T; Li, J; Wang, Y-Y; Liu, B-Y
Chinese herbal medicine Jinlianqingre Effervescent Tablets (JET) are the recommended control measure for uncomplicated hand, foot, and mouth disease (HFMD) by the Ministry of Health of China. However, high-quality evidence to support this recommendation is limited. A total of 288 patients ranging in age from 1 to 13 years were randomly assigned to JET in combination with conventional therapy (mainly including the reduction of temperature by applying physical cooling paste or warm bathing), or conventional therapy with placebo group for 7 days. The objective was to test the hypothesis that JET combination therapy is more effective than conventional therapy for uncomplicated HFMD. A randomized, double-blind, placebo-controlled trial was designed. Our study showed that, compared with conventional therapy, the median time to fever resolution was significantly shorter in the JET combination therapy (8 vs. 80 h; p < 0.0001); the risk of fever resolution increased in the JET combination therapy [hazard ratio, 19.8; 95% confidence interval (CI), 12.8 to 30.7]; the median healing time of rash or oral ulcer was significantly shorter in the JET combination therapy (14 vs. 74 h; p < 0.0001); and the median symptom score for skin or oral mucosa lesions improved more rapidly in the JET combination therapy during the follow-up period. The median duration of hospital stay was 6 days in the JET combination therapy and 7 days in the conventional therapy (p < 0.0001). No significant adverse events and complications were found in both groups. The addition of JET to conventional therapy reduced fever clearance time, healing time of skin or oral mucosa lesions, and duration of hospital stay in children with uncomplicated HFMD.
Full Text Available Signal processing methods based on the combined use of the continuous wavelet transform (CWT and zero-crossing technique were applied to the simultaneous spectrophotometric determination of perindopril (PER and indapamide (IND in tablets. These signal processing methods do not require any priory separation step. Initially, various wavelet families were tested to identify the optimum signal processing giving the best recovery results. From this procedure, the Haar and Biorthogonal1.5 continuous wavelet transform (HAAR-CWT and BIOR1.5-CWT, respectively were found suitable for the analysis of the related compounds. After transformation of the absorbance vectors by using HAAR-CWT and BIOR1.5-CWT, the CWT-coefficients were drawn as a graph versus wavelength and then the HAAR-CWT and BIOR1.5-CWT spectra were obtained. Calibration graphs for PER and IND were obtained by measuring the CWT amplitudes at 231.1 and 291.0 nm in the HAAR-CWT spectra and at 228.5 and 246.8 nm in BIOR1.5-CWT spectra, respectively. In order to compare the performance of HAAR-CWT and BIOR1.5-CWT approaches, derivative spectrophotometric (DS method and HPLC as comparison methods, were applied to the PER-IND samples. In this DS method, first derivative absorbance values at 221.6 for PER and 282.7 nm for IND were used to obtain the calibration graphs. The validation of the CWT and DS signal processing methods was carried out by using the recovery study and standard addition technique. In the following step, these methods were successfully applied to the commercial tablets containing PER and IND compounds and good accuracy and precision were reported for the experimental results obtained by all proposed signal processing methods.
Łaszcz, Marta; Witkowska, Anna
Studies of the phase transitions in an active substance contained in a solid dosage form are very complicated but essential, especially if an active substance is classified as a BCS Class IV drug. The purpose of this work was the development of sensitive methods for the detection of the phase transitions in the aripiprazole tablets containing initially its form III. Aripiprazole exhibits polymorphism and pseudopolymorphism. Powder diffraction, Raman spectroscopy and differential scanning calorimetry methods were developed for the detection of the polymorphic transition between forms III and I as well as the phase transition of form III into aripiprazole monohydrate in tablets. The study involved the initial 10 mg and 30 mg tablets, as well as those stored in Al/Al blisters, a triplex blister pack and HDPE bottles (with and without desiccant) under accelerated and long term conditions. The polymorphic transition was not observed in the initial and stored tablets but it was visible on the DSC curve of the Abilify(®) 10 mg reference tablets. The formation of the monohydrate was observed in the diffractograms and Raman spectra in the tablets stored under accelerated conditions. The monohydrate phase was not detected in the tablets stored in the Al/Al blisters under long term conditions. The results showed that the Al/Al blisters can be recommended as the packaging of the aripiprazole tablets containing form III. Copyright © 2015 Elsevier B.V. All rights reserved.
Obeidat, Wasfy M; Nokhodchi, Ali; Alkhatib, Hatim
The purpose of this work was to investigate the influence of Eudragit®E100 polymer in modifying the release rates and compaction properties of water soluble model drug paracetamol from Carbopol®971P NF polymer matrix tablets prepared by direct compression. The effects of the ratio of the two polymers, the total polymeric content, and the tablets mechanical strength on paracetamol release rates were investigated. Dissolution studies were conducted using USP XX Π rotating paddle apparatus at 50 rpm and 37°C at three different stages (pH 1.2, 4.8, and 6.8). Results showed that the polymers combination improved significantly the compaction properties of paracetamol tablets as evident by the higher crushing strengths (8.3 ± 0.4 Kp) compared to polymer-free tablets (3.4 ± 0.2 Kp) at intermediate compression pressure of 490 MPa. When combined with Carbopol®971P NF, Eudragit®E100 was found to be capable of extending paracetamol release for more than 12 h compared to 1 h for polymers-free tablets. The combined polymers were able to control paracetamol release in a pH independent pattern. The f2 (similarity factor) analysis showed that the ratio between the polymers and the total polymer concentration exhibited significant impact on drug release rates. In conclusion, Eudragit®E100 when combined with Carbopol®971P NF was capable of improving the compaction and sustained release properties of paracetamol. Korsmeyer-Peppas model was found to be the most suitable for fitting drug release data. The polymer combinations can potentially be used to control the release rates of highly water soluble drugs.
Brniak, Witold; Maślak, Ewelina; Jachowicz, Renata
Orodispersible tablets (ODTs) and orodispersible films (ODFs) are solid oral dosage forms disintegrating or dissolving rapidly when placed in the mouth. One of the main issues related to their preparation is an efficient taste masking of a bitter drug substance. Therefore, the aim of this study was to prepare and evaluate the microparticles intended to mask a bitter taste of the prednisolone and use them in further preparation of two orodispersible dosage forms. Microparticles based on the Eudragit E PO or E 100 as a taste-masking agent were prepared with spray-drying technique. Tablets containing microparticles, co-processed ODT excipient Pharmaburst, and lubricant were directly compressed with single-punch tablet press. Orodispersible films were prepared by casting polymeric solutions of hydroxypropyl methylcellulose containing uniformly dispersed microparticles. Physicochemical properties of microparticles were evaluated, as well as mechanical properties analysis, disintegration time measurements and dissolution tests were performed for prepared dosage forms. Both formulations showed good mechanical resistance while maintaining excellent disintegration properties. The dissolution studies showed good masking properties of microparticles with Eudragit E 100. The amount of prednisolone released during the first minute in phosphate buffer 6.8 was around 0.1%. After incorporation into the orodispersible forms, the amount of released prednisolone increased significantly. It was probably the effect of faster microparticles wetting in orodispersible forms and their partial destruction by compression force during tableting process. Copyright © 2015 Elsevier B.V. All rights reserved.
Zhao, Na; Zidan, Ahmed; Tawakkul, Mobin; Sayeed, Vilayat A; Khan, Mansoor
Metoprolol succinate extended release tablets comprise a multiple unit system containing metoprolol succinate in a multitude of controlled release pellets. Each pellet acts as a separate drug delivery unit and is designed to deliver metoprolol continuously over the dosage interval. Despite the flexibility that controlled release pellets may offer, segregation is one of the challenges that commonly occur during tableting for such drug delivery system. Since all commercial metoprolol succinate extended release tablets are scored, they are deemed suitable for splitting. The present study was aimed at utilizing an innovative technology to determine the dose uniformity for split tablets. Four marketed drug products consisting of innovator and generics were evaluated for effect of splitting on weight, assay and content uniformity. Novel analytical tool such as near infrared (NIR) chemical imaging was used to visualize the distribution of metoprolol succinate and functional excipients on the surfaces of the marketed tablets. The non-homogeneous distribution of directly compressed metoprolol succinate beads on the surface of the tablets as well as the split intersection explained the large variation in the split tablets' weight and content uniformity results. The obtained results indicated the usefulness of NIR chemical imaging to determine the need for content uniformity studies for certain split tablets. Published by Elsevier B.V.
Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.
Darwish Hany W.
Full Text Available Simultaneous spectrophotometric analysis of a multi-component dosage form of olmesartan, amlodipine and hydrochlorothiazide used for the treatment of hypertension has been carried out using various chemometric methods. Multivariate calibration methods include classical least squares (CLS executed by net analyte processing (NAP-CLS, orthogonal signal correction (OSC-CLS and direct orthogonal signal correction (DOSC-CLS in addition to multivariate curve resolution-alternating least squares (MCR-ALS. Results demonstrated the efficiency of the proposed methods as quantitative tools of analysis as well as their qualitative capability. The three analytes were determined precisely using the aforementioned methods in an external data set and in a dosage form after optimization of experimental conditions. Finally, the efficiency of the models was validated via comparison with the partial least squares (PLS method in terms of accuracy and precision.
FELICIA G. GLIGOR
Full Text Available Several tablet formulations containing silymarin were developed, in order to meet the requirements of different markets. Milk thistle - Silybum marianum (L. Gaertn – standardized extracts have proven their positive effect on liver functionality plus other health benefits. Lactose is a widely used excipient for the production of oral solid dosage forms. One important inconvenient of lactose is related to the lactose intolerant potential customers. Cellulose, isomalt and dicalcium phosphate have been selected as alternative possible tablet binders and diluents. Laboratory and pilot batches were studied for each excipient. The pharmacotechnical properties and silybin content of the tablets were measured and recorded in accordance to the European Pharmacopoeia. All pilot batches had results in the desired range of values in order to permit large scale compacting and blistering of the tablets. Currently the formulations containing isomalt and dicalcium phosphate that made the subject of this study are being produced on industrial scale.
Background Metronidazole (MET) and Diloxanide Furoate (DF), act as antiprotozoal drugs, in their ternary mixtures with Mebeverine HCl (MEH), an effective antispasmodic drug. This work concerns with the development and validation of two simple, specific and cost effective methods mainly for simultaneous determination of the proposed ternary mixture. In addition, the developed multivariate calibration model has been updated to determine Metronidazole benzoate (METB) in its binary mixture with DF in Dimetrol® suspension. Results Method (I) is the mean centering of ratio spectra spectrophotometric method (MCR) that depends on using the mean centered ratio spectra in two successive steps that eliminates the derivative steps and therefore the signal to noise ratio is enhanced. The developed MCR method has been successfully applied for determination of MET, DF and MEH in different laboratory prepared mixtures and in tablets. Method (II) is the partial least square (PLS) multivariate calibration method that has been optimized for determination of MET, DF and MEH in Dimetrol ® tablets and by updating the developed model, it has been successfully used for prediction of binary mixtures of DF and Metronidazole Benzoate ester (METB) in Dimetrol ® suspension with good accuracy and precision without reconstruction of the calibration set. Conclusion The developed methods have been validated; accuracy, precision and specificity were found to be within the acceptable limits. Moreover results obtained by the suggested methods showed no significant difference when compared with those obtained by reported methods. Graphical Abstract PMID:22475262
Abdelaleem Eglal A
Full Text Available Abstract Background Metronidazole (MET and Diloxanide Furoate (DF, act as antiprotozoal drugs, in their ternary mixtures with Mebeverine HCl (MEH, an effective antispasmodic drug. This work concerns with the development and validation of two simple, specific and cost effective methods mainly for simultaneous determination of the proposed ternary mixture. In addition, the developed multivariate calibration model has been updated to determine Metronidazole benzoate (METB in its binary mixture with DF in Dimetrol® suspension. Results Method (I is the mean centering of ratio spectra spectrophotometric method (MCR that depends on using the mean centered ratio spectra in two successive steps that eliminates the derivative steps and therefore the signal to noise ratio is enhanced. The developed MCR method has been successfully applied for determination of MET, DF and MEH in different laboratory prepared mixtures and in tablets. Method (II is the partial least square (PLS multivariate calibration method that has been optimized for determination of MET, DF and MEH in Dimetrol ® tablets and by updating the developed model, it has been successfully used for prediction of binary mixtures of DF and Metronidazole Benzoate ester (METB in Dimetrol ® suspension with good accuracy and precision without reconstruction of the calibration set. Conclusion The developed methods have been validated; accuracy, precision and specificity were found to be within the acceptable limits. Moreover results obtained by the suggested methods showed no significant difference when compared with those obtained by reported methods. Graphical Abstract
The calculation of dosages in paediatrics is the concern of the whole medical and paramedical team. This activity must generate a minimum of risks in order to prevent care-related adverse events. In this context, the calculation of dosages is a practice which must be understood by everyone. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Hogue, Rebecca J.
This paper discusses the scholarly literature related to tablet computer use in medicine. Forty-four research-based articles were examined for emerging categories and themes. The most studied uses for tablet computers include: patients using tablets to complete diagnostic survey instruments, medical professionals using tablet computers to view…
Petri, J; Kaunzinger, A; Niemöller, A; Karas, M
Today, NIR-spectroscopy is an established analytical technique not only in the identification of raw materials but also in the quantification of active ingredients in tablets. In this work calibration models were set up with tablets of the same active ingredient but of miscellaneous origin and manufacturess. Consequently the tablets had different excipients and appearance. The pharmaceutical preparations used included atenolol 100 mg tablets, enalapril 20 mg tablets and acetylsalicylic acid (ASS) tablets of different dosage units. In order to proof if the calibration models set up are generally feasible the assay declared by the manufacturer was used to calculate the partial least square (PLS) calibration. With respect to enalapril tablets simultaneous analysis by HPLC, according to USP 26 was carried out. It was investigated if such methods allow a determination of active ingredients in tablets within limits of +/- 10% of declaration. It was shown that it is possible to set up calibration models to quantify active ingredients in tablets independent of adjuvants or optical appearance. Additionally it could be shown that NIR-spectroscopy is also applicable to determine the concentration of active ingredients in blister-packed tablets.
Ridgway, Cathy; Bawuah, Prince; Markl, Daniel; Zeitler, J Axel; Ketolainen, Jarkko; Peiponen, Kai-Erik; Gane, Patrick
The physical properties and mechanical integrity of pharmaceutical tablets are of major importance when loading with active pharmaceutical ingredient(s) (API) in order to ensure ease of processing, control of dosage and stability during transportation and handling prior to patient consumption. The interaction between API and excipient, acting as functional extender and binder, however, is little understood in this context. The API indomethacin is combined in this study with microcrystalline cellulose (MCC) at increasing loading levels. Tablets from the defined API/MCC ratios are made under conditions of controlled porosity and tablet thickness, resulting from different compression conditions, and thus compaction levels. Mercury intrusion porosimetry is used to establish the accessible pore volume, pore size distribution and, adopting the observed region of elastic intrusion-extrusion at high pressure, an elastic bulk modulus of the skeletal material is recorded. Porosity values are compared to previously published values derived from terahertz (THz) refractive index data obtained from exactly the same tablet sample sets. It is shown that the elastic bulk modulus is dependent on API wt% loading under constant tablet preparation conditions delivering equal dimensions and porosity. The findings are considered of novel value in respect to establishing consistency of tablet production and optimisation of physical properties. Copyright © 2017 Elsevier B.V. All rights reserved.
Galande, Varsha R; Baheti, K G; Indraksha, S; Dehghan, M H
A simple, precise, accurate and economic simultaneous UV spectrophotometric method has been developed for the estimation of amlodipine besylate, valsartan and hydrochlorothiazide in combination in bulk mixture and tablet. The estimation was based upon measurement of absorbance at absorbance maxima of 359 nm, 317 nm and 250 nm for amlodipine besylate, hydrochlorothiazide and valsartan in methanol, respectively in bulk mixture and tablet. The Beer Lambert's law obeyed in the concentration range 5-25 μg/ml, 10-50 μg/ml and 5-25 μg/ml for amlodipine besylate, hydrochlorothiazide and valsartan, respectively. The estimation of bulk mixture and tablet was carried out by simultaneous equation, Q-analysis and area under curve method for estimation of amlodipine besylate and hydrochlorothiazide and standard curve method for estimation of valsartan. The results were found to be in the range of 99.6±1.52% to 102±0.51%. Method was validated with respect to specificity, linearity, range, accuracy, precision, LOD, LOQ, robustness, ruggedness and can be applied for routine analysis of tablet dosage forms.
Khan, Lubna Ghazal; Razvi, Nighat; Anjum, Fakhsheena; Siddiqui, Saeed Ahmed; Ghayas, Sana
This study was conducted to assess the effects of various excipients in 10 different Tizanidine hydrochloride tablet dosage forms that were prepared by direct compression method (DC). Various excipients are available for DC method; we selected those excipients that are used commonly in tablet manufacturing. The excipients used included lactose anhydrous, di-basic calcium phosphate anhydrous, starch, talc, sodium carboxy methyl cellulose, polyvinyl pyrrolidone (PVP), silicon dioxide (Aerosil), stearic acid, magnesium stearate and microcrystalline cellulose (Avicel). These tablets were then evaluated by performing different pharmacopoeial and non-pharmacopoeial tests (i.e. diameter, hardness, thickness, weight variation, disintegration and assay). It was observed that Formulations B, D and H of Tizanidine hydrochloride gave best results within USP specified limits for the tests employed among all the formulations whereas Formulations F and G showed poor friability, disintegration and dissolution profiles rendering starch in combination of talc and sodium carboxy-methyl cellulose unsuitable for Tizanidine hydrochloride tablet formulations. With the present approach, more studies can be designed using other active ingredients and excipients to get an optimal and cost effective product.
... response within 2 to 3 days, reevaluate therapy. Do not crush tablets. Treated animals must not be... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520...
Full Text Available Roll compaction was applied for the preparation of hydroxypropyl cellulose (HPC-based sustained-release matrix tablets. Matrix tablets made via roll compaction exhibited higher dosage uniformity and faster drug release than direct-compacted tablets. HPC viscosity grade, roll pressure, and milling speed affected tablet properties significantly. Roll compaction seems to be an adequate granulation method for the preparation of HPC-based matrix tablets due to the simplicity of the process, less handling difficulty from HPC tackiness as well as easier particle size targeting. Selecting the optimum ratio of plastic excipients and the particle size of starting materials can however be critical issues in this method.
Zaazaa, Hala E; Elzanfaly, Eman S; Soudi, Aya T; Salem, Maissa Y
Ratio difference spectrophotometric method was developed for the determination of ibuprofen and famotidine in their mixture form. Ibuprofen and famotidine were determined in the presence of each other by the ratio difference spectrophotometric (RD) method where linearity was obtained from 50 to 600μg/mL and 2.5 to 25μg/mL for ibuprofen and famotidine, respectively. The suggested method was validated according to ICH guidelines and successfully applied for the analysis of ibuprofen and famotidine in their pharmaceutical dosage forms without interference from any additives or excipients. Copyright © 2015 Elsevier B.V. All rights reserved.
Zaazaa, Hala E.; Elzanfaly, Eman S.; Soudi, Aya T.; Salem, Maissa Y.
Ratio difference spectrophotometric method was developed for the determination of ibuprofen and famotidine in their mixture form. Ibuprofen and famotidine were determined in the presence of each other by the ratio difference spectrophotometric (RD) method where linearity was obtained from 50 to 600 μg/mL and 2.5 to 25 μg/mL for ibuprofen and famotidine, respectively. The suggested method was validated according to ICH guidelines and successfully applied for the analysis of ibuprofen and famotidine in their pharmaceutical dosage forms without interference from any additives or excipients.
Tablet that disintegrate rapidly in the mouth are convenient for patient who have difficulty in swallowing conventional dosages forms. Although various formulation technologies like Zydis Technology, Durasolve Technology, Orasolve Technology, Flash Dose Technology, Wow Tab Technology, Flash Tab Technology, Quicksolv Technology, Lyos Technology, Fast Melt Technology and Zip-lets Technology are used. This review highlights numerous techniques to explain the phenomenon of preparing mouth disinte...
Montero-Padilla, Soledad; Velaga, Sitaram; Morales, Javier O
The development of an appropriate dosage form for pediatric patients needs to take into account several aspects, since adult drug biodistribution differs from that of pediatrics. In recent years, buccal administration has become an attractive route, having different dosage forms under development including tablets, lozenges, films, and solutions among others. Furthermore, the buccal epithelium can allow quick access to systemic circulation, which could be used for a rapid onset of action. For pediatric patients, dosage forms to be placed in the oral cavity have higher requirements for palatability to increase acceptance and therapy compliance. Therefore, an understanding of the excipients required and their functions and properties needs to be particularly addressed. This review is focused on the differences and requirements relevant to buccal administration for pediatric patients (compared to adults) and how novel dosage forms can be less invasive and more acceptable alternatives.
Full Text Available In this study, the electrochemical reduction and determination of metronidazole were easily realized in Britton-Robinson buffer (pH = 4.01 using UTGE by cyclic voltammetric (CV and differential pulse voltammetric (DPV techniques. In this acidic medium, one irreversible and sharp cathodic peak was observed. A linear calibration curve for DPV analysis was constructed in the metronidazole concentration range 3x10-6 - 9x 10-5 mol L-1. Limit of detection (LOD and limit of quantification (LOQ were 1.42x10-7 and 4.76x10-7 mol L-1 respectively.
Metoprolol, a beta-1 selective adrenegic receptor blocker antihypertensive agent is fairly new in Nigeria. In view of the endemic faking and adulterating of drugs in Nigeria, a simple, quick, and accurate method was developed for its assay. Metoprolol was coupled with 4-chloro-7-nitrobenzo-2-oxa-1, 3 diazole (NBD-Cl) in ...
Y. Ankamma Chowdary
Full Text Available In the treatment of type 2 diabetes mellitus a continuous therapy is required which is a more complex one. As in these patients there may be a defect in both insulin secretion and insulin action exists. Hence, the treatment depends on the pathophysiology and the disease state. In the present study, multilayered tablets of pioglitazone hydrochloride 15 mg and metformin hydrochloride 500 mg were prepared in an attempt for combination therapy for the treatment of type 2 diabetes mellitus. Pioglitazone HCl was formulated as immediate release layer to show immediate action by direct compression method using combination of superdisintegrants, namely, crospovidone and avicel PH 102. Crospovidone at 20% concentration showed good drug release profile at 2 hrs. Metformin HCl was formulated as controlled release layer to prolong the drug action by incorporating hydrophilic polymers such as HPMC K4M by direct compression method and guar gum by wet granulation method in order to sustain the drug release from the tablets and maintain its integrity so as to provide a suitable formulation. The multilayered tablets were prepared after carrying out the optimization of immediate release layer and were evaluated for various precompression and postcompression parameters. Formulation F13 showed 99.97% of pioglitazone release at 2 hrs in 0.1 N HCl and metformin showed 98.81% drug release at 10 hrs of dissolution in 6.8 pH phosphate buffer. The developed formulation is equivalent to innovator product in view of in vitro drug release profile. The results of all these evaluation tests are within the standards. The procedure followed for the formulation of these tablets was found to be reproducible and all the formulations were stable after accelerated stability studies. Hence, multilayered tablets of pioglitazone HCl and metformin HCl can be a better alternative way to conventional dosage forms.
Buck, Jonas; Huwyler, Jörg; Kühl, Peter; Dischinger, Angela
The design of pediatric formulations is challenging. Solid dosage forms for children have to meet the needs of different ages, e.g. high number of dosing increments and strengths. A modular formulation strategy offering the possibility of rapid prototyping was applied. Different tablet compositions and the resulting tablet characteristics were investigated for dispersible tablets using customized analytical methods. Fluid bed granules were blended with extragranular components, and compressed to tablets. Disintegration behavior was studied with a Texture Analyzer and a Tensiometer. Methods for determination of disintegration time and water uptake of tablets were developed with a Texture Analyzer, and a Tensiometer, respectively. Twenty-two different tablet formulations were prepared and analyzed with respect to disintegration time, hardness, friability, and viscosity. Multivariate data analysis revealed a high impact of type and amount of viscosity enhancer on the disintegration behavior of tablets. An optimized formulation was selected with a disintegration time of 24 s. Methods providing additional information on the disintegration behavior of dispersible tablets compared to standard pharmacopoeia methods were established. Selecting the right type and level of viscosity enhancer and superdisintegrant was critical for developing pediatric tablets with a disintegration time of less than 30 s but still pleasant mouth feel.
Shahtalebi Mohammad Ali; Tabbakhian Majid; Koosha Sina
Introduction: Difficulty in swallowing is common among all age groups, especially elderly and pediatrics. Orally disintegrating tablets may constitute an innovative dosage form that overcome the problem of swallowing and provide a quick onset of action. This study was aimed to formulate and evaluate an orally disintegrating tablet (ODT) containing ondansetron while using semi-synthetic and natural superdisintegrants. Methods: Orodispersible tablets were prepared by direct compression using na...
Each type of granules was compressed to tablets of weight 100, 150 or 200mg. To form the multi-unit dosage tablets of drug content 300mg each, the conventional and matrix granules were mixed in the ratio 1:2, 1:1 and 2:1, and compressed. The tablets were subjected to dissolution test and from the experimental release ...
Fuchs, Uwe; Zittermann, Armin; Ensminger, Stephan M; Schulz, Uwe; Gummert, Jan F
The mTOR inhibitor everolimus (EVL) can be used for calcineurin inhibitor-sparing immunosuppression in heart transplantation (HTx). However, comparable data regarding clinical outcomes in HTx recipients receiving EVL either with dosage reduction of cyclosporine A (CSA) or with dosage reduction of tacrolimus (TAC) is scarce. In a retrospective data analysis, we compared 5-year clinical outcomes in 154 maintenance patients receiving EVL with CSA (n=106) or TAC (n=48). The primary endpoint was a composite of death, graft loss and EVL discontinuation (treatment failure). Secondary endpoints were kidney function, cardiac rejection, cytomegalovirus infection and biochemical safety parameters. In the CSA and TAC group, the primary endpoint was reached by 59.8% and 53.1%, respectively (P=0.716). Five-year mortality was 30.4% (CSA group) and 23.13% (TAC group), respectively (P=0.371), and freedom from EVL discontinuation was 53.3% and 59.6% (P=0.566) in the respective groups. Covariate-adjusted relative risk of treatment failure was in the CSA group=1.28 (95% CI: 0.70-2.34; P=0.43) compared with the TAC group. The course of covariate-adjusted estimated glomerular filtration rate and freedom from cytomegalovirus infection was similar in the two groups (P=0.502 and P=0.476), whereas covariate-adjusted freedom from rejection was lower in the CSA group compared with the TAC group (P=0.023). Lipid status and blood cell counts were comparable between groups. In conclusion, data indicate that EVL plus reduced TAC is not superior to EVL plus reduced CSA regarding treatment failure and kidney function. However, compared with EVL plus reduced CSA, EVL plus reduced TAC seems to reduce cardiac rejections. Copyright © 2014 Elsevier B.V. All rights reserved.
Abduljabbar, Hana N; Badr-Eldin, Shaimaa M; Aldawsari, Hibah M
Ranitidine HCl is an H2-antagonist that suffers from low oral bioavailability of 50%. The site-specific absorption from the upper part of the small intestine and the colonic metabolism of the drug could partially contribute to its reduced bioavailability. To surmount these drawbacks, this work aimed at the formulation of Ranitidine HCl gastroretentive floating-biaodhesive tablets. A 3(2) factorial design was applied to assess the effects of matrix former (HPMC K100M): drug ratio, and the release retardant (Carbopol 971) amount on the characteristics of the tablets prepared using direct compression technique. The prepared tablets were thoroughly evaluated for physical properties, floating, swelling, bioadhesive and in vitro release behaviors. Statistical analysis of the results revealed significant effects for both formulation variables on the swelling index, maximum detachment force and cumulative percent drug released after 6 hours. In addition, the matrix- former: drug ratio showed a statistically significant effect on the floating lag time. Kinetic analysis of the release data indicated Higuchi diffusion kinetics and anomalous transport mechanism for all formulations. Scanning electron micrographs of the selected tablet formulation; F8, revealed intact surface without any perforations or channels in the dry state, while polymer expansion (relaxation) with some perforated areas were observed on the surface of the tablets after 12 hours dissolution in 0.1 N HCl. Furthermore, in vivo abdominal x-ray imaging showed good floating behavior of the selected formulation; F8, for up to 6 hours with appropriate bioadhesive property. In conclusion, the selected ranitidine HCl floating-bioadhesive tablets could be regarded as a promising gastroretentive drug delivery system that could deliver the drug at a controlled rate.
Liu, M; Wang, X L; Zhang, D; Yang, M; Han, J; Zhang, Y N; Wang, Z L; Liu, H C
A fixed dose combination tablet of niacin extended release (ER)/simvastatin was recently developed in China. This study was designed to assess and compare the pharmacokinetics of niacin, simvastatin and their metabolites in healthy Chinese subjects after single and multiple doses administration. From day 1 to day 7, 12 Chinese subjects were given a tablet every day at approximately 10 p.m. Serial blood samples were collected. Niacin and nicotinuric acid (NUA) in plasma, niacin, NUA, N-methylnicotinamide (MNA) and N-methyl-2-pyridone-5-carboxamide (2PY) in urine, simvastatin and simvastatin acid in plasma were determined by LC/MS/MS methods. Pharmacokinetic parameters on days 1 and 7 were compared. The main pharmacokinetic parameters for the single and multiple doses were as -follows: Niacin: Tmax were 3.8±1.5 h and 3.9±2.0 h; Cmax were 2 091±1 315 ng/ml and 2 323±1 542 ng/ml; AUC0-t were 4 123.88±3 138.48 ng ∙ h/ml and 4 385.98±3 127.05 ng ∙ h/ml. NUA: Tmax were 4.7±1.7 h and 3.8±1.5 h; Cmax were 1 057±549 ng/ml and 1 087±470 ng/ml; AUC0-t were 4 012.49±2 168.68 ng ∙ h/ml and 4 040.45±1 886.57 ng ∙ h/ml. Simvastatin: Tmax were 1.8±1.0 h and 2.5±2.5 h; Cmax were 3.15±1.67 ng/ml and 4.87±4.11 ng/ml; AUC0-t were 9.03±5.10 ng ∙ h/ml and 17.63±13.93 ng ∙ h/ml. Simvastatin acid: Tmax were 5.8±1.7 h and 6.5±1.4 h; Cmax were 4.22±2.10 ng/ml and 9.30±8.09 ng/ml; AUC0-t were 34.65±16.89 ng ∙ h/ml and 61.62±46.41 ng ∙ h/ml. Urine Recovery rate of total niacin: (40.55±7.38)% and (62.87±12.04)%. Compared with those after a single dose, pharmacokinetics of niacin and NUA was similar; total urine recovery of niacin was higher; exposure to simvastatin and simvastatin acid were higher following multiple doses. © Georg Thieme Verlag KG Stuttgart · New York.
Lee, Ah Ram; Kwon, Seok Young; Choi, Du Hyung; Park, Eun Seok
A bilayer tablet, which consisted of telmisartan and amlodipine besylate, was formulated based on a Quality by Design (QbD) approach. The control and response factors were determined based on primary knowledge and the target values of the control tablet (Twynsta(®)). A D-optimal mixture design was used to obtain the optimal formulations in terms of D-mannitol, crospovidone, and MCC for the telmisartan layer, and CCM-Na, PVP K25, and Prosolv for the amlodipine layer. The quantitative effects of the different formulation factors on the response factors were accurately predicted using the equations of best fit and a strong linearity was observed between the predicted and actual values of the response factors. The optimized bilayer tablet was obtained using a numeric optimization technique and was characterized compared with a control (Twynsta(®)) by using various physical evaluations and in vivo pharmacokinetic parameters. The physical stability of Telmiduo(®) was greater than that of Twynsta(®) owing to the improvement of formulation factors. The in vivo pharmacokinetic parameters suggested that Telmiduo(®) might have pharmaceutical equivalence and bioequivalence with Twynsta(®). Therefore, the bilayer tablet that consisted of telmisartan and amlodipine besylate could be produced using a more economical and simpler method than that used to produce Twynsta(®). Moreover, the suitability of QbD for effective product development in the pharmaceutical industry was shown. Copyright © 2017 Elsevier B.V. All rights reserved.
A. S. Inhã
Full Text Available A medicament is defined as a pharmaceutical product that is obtained or prepared technologically. It should contain one or more active ingredients with other substances with prophylactic, curative, palliative or diagnostic purposes. The pharmaceutical dosage form of oral tablets is relevant given the advantages it presents. The drugs are produced in pre-established doses, doses that are patterns of each pharmaceutical company and may not meet the needs of all patients. There is still a need to reduce the cost or achieve lower dosages that are sometimes found not commercially available and therefore, frequently some patients are instructed to cut the tablets. ANVISA reports that the practice of tablets partition in half is harmful to the patient, especially if the tablet has some special kinds of releasing its contents, in a given period or location in the body, before dissolving completely or whether they have coatings. This work aims to analyze the partition of propranolol and atenolol tablets, and if the process of partition can influence in the uniformity of the drug between the halves obtained after splitting using the employment tablet cutters. These tablets Propranolol 40mg and Atenolol 50mg were chosen due to their common use to control blood pressure. The assay methodology of these active ingredients has been adapted from Brazilian Pharmacopoeia (1988 using spectrophotometry. The results showed that there was a variation in the dosage of atenolol tablets parties from 70-142% and for propranolol half tablets the variation was obtained around 90 and 112% of the half dosage. Propranolol data may have been better since these tablet shave a facilitator who is the divisor groove. The data indicate that the partition tablets should not be encouraged because it can lead to loss of efficacy in the treatment.
Gururaj S.Kulkarni; N.G RaghavendraRao; D.Narasimhareddy
The main objective of developing any new dosage form is reduce the side effects and increase the therapeutic effect of drug in existing dose of dosage form. Mucoadhesive drug delivery system is oral dosage form, where the tablet, gel or patch is attached to the buccal region for direct absorption of drug into blood circulation. This route can prevent the metabolism of drug in G.I tract or liver and side effects of metabolites avoided. In this study, the attempt was made to prepare mucoadhesiv...
materials, packaging materials, personnel that come in contact with the product during the manufacturing process ... Twenty two different brands of tablet dosage forms that contained 8 pharmaceutical active ingredients were ... and their drugs approved by the Jordan Food and Drug Administration (JFDA). For each brand,.
Purpose: To develop a simple and selective isocratic method for the determination of venlafaxine and modafinil in tablet dosage forms. Methods: The compounds were analyzed on Waters symmetry C18 column (4.6 mm x 250 mm i.d, 5ìm) using a mobile phase consisting of a mixture of ammonium acetate buffer (pH was ...
Purpose: To develop a simple and selective isocratic method for the determination of venlafaxine and modafinil in tablet dosage forms. Methods: The compounds were analyzed on Waters symmetry C18 column (4.6 mm x 250 mm i.d,. 5µm) using a mobile phase consisting of a mixture of ammonium acetate buffer (pH was ...
Sulaiman, T.N. Saifullah; Puspita, Desi Elvira Cindy; Wahyono, Wahyono
Senggugu root bark (Clerodendrum serratum L. Moon) is known as a mucolitics. Senggugu root bark is made in the dosage form of lozenges in combination with sucrose, mannitol and lactose in order to obtain good flavor and comfortable when consumed. The purpose of this study was to determine the effect of the combination of fillers on the physical properties of granules and tablets as well as the composition of the combination of excipients to produce lozenges of extract of senggugu root bark wi...
Rane Rajashree; Gangolli Divya; Patil Sushma; Ingawale Kanchan; Kundalwal Sachin
Different dosage forms namely tablets, capsules, creams and syrups were analysed for curcumin content, by the well-known spectrophotometric method. Turmeric extract powder was used as a source of curcumin in capsule and tablet formulations. Turmeric oleoresin was used as a source of curcumin in cream formulation. Additionally, syrup formulations containing turmeric extract powder as well as turmeric oleoresin, separately, were also tested for their curcumin contents. Analytical results for cu...
Full Text Available Orally disintegrating tablets (ODTs are dosage forms which disintegrate in mouth within seconds without need of water. This type of quality in dosage form can be attained by addition of different varieties of excipients. Pharmaburst™ 500 is a co-processed excipient system which allows rapid disintegration and low adhesion to punches. The aim of the present study was to develop and evaluate 25 mg diclofenac sodium ODTs (orodispersible tablets batches by direct compression method at different compression forces 10 kN (F1 and 20 kN (F2 and directly compressible excipients used in different ratio (Avicel PH 102, magnesium stearate and coprocessed excipient Pharmaburst™ 500, 70% and 80% w/w. The obtained batches were analyzed for appearance, tablet thickness, uniformity of weight, hardness, friability, disintegration time, and non-compendial methods (wetting time. Co-processed Pharmaburst™ 500 excipient 70% used for sodium diclofenac ODT obtaining determined good results for quality control tests evaluation.
Frijlink, Henderik W.; Hinrichs, Wouter; Grasmeijer, Floris
The present invention relates to dosage forms comprising a compressed blend of a biologically active ingredient, one or more polymers like a poly(α-hydroxy carboxylic acid) in which optionally is incorporated a glass transition modifying agent, and optional further ingredients, wherein the polymer
Huang, Haiqin; Wu, Zhenghong; Qi, Xiaole; Zhang, Huiting; Chen, Qin; Xing, Jiayu; Chen, Haiyan; Rui, Yao
Compression coating, which presents some advantages like short manufacturing process and non-solvent residue over liquid coating, has been introduced to the oral administration systems for decades. The purpose of this study was to design a zero-order release of compression-coated tablets using hydroxypropylcellulose (HPC) as the coating layer and glipizide which was solubilized by manufacturing the inclusion complex of β-cyclodextrin as a model drug. The effects of the weight ratio of drug and the viscosity of HPC on the release profile were investigated by "f2" factor with Glucotrol XL(®). The uptake and erosion study, the correlation coefficient (R) and the exponent (n) were used as indicators to justify drug release mechanism. Bioavailability in vivo was determined by administering the compression-coated tablets to rabbits in contrast with Glucotrol XL(®). It was found that the formulation presented a well zero-order behavior at the weight ratio of drug 11:14 (core:layer) and the combination of HPC-L (8.0 mPa s) and HPC-M (350 mPa s) (8:9), with the "f2" of 66.90. The mechanism for zero-order release of these compression-coated tablets was solvent penetration into the dosage form and drug dissolution from the erosion of the gelled HPC matrix. The parameter AUC0-∞ of the compression coated tablets and the market tablets were 37,255.93±1474.08 h ng/ml and 43265.40±1015.28 h ng/ml, while the relative bioavailability was 87.66±1.56%. These studies demonstrate that the designed compression-coated tablets may be a promising strategy for peroral controlled release delivery system of water-insoluble drugs. Copyright © 2013 Elsevier B.V. All rights reserved.
Muller, Claudia; Mazel, Vincent; Dausset, Caroline; Busignies, Virginie; Bornes, Stéphanie; Nivoliez, Adrien; Tchoreloff, Pierre
The beneficial effects of probiotic bacteria on human health are now widely acknowledged, and this has prompted growing interest in research and development in the pharmaceutical field. However, to be viable when they reach their target, the bacteria must be able to survive during the manufacturing process and the biological pathway. Tablet form best meets the requirements for protecting acid labile drugs, but the tableting process could be an additional stress for the bacteria. This study evaluated the initial effect of compression pressure on the Lcr35® strain in a vaginal (Lcr regenerans®) and an intestinal (Lcr restituo®) formulation. A stability study was also performed on the tablets and revealed a beneficial effect of this form. The obtained destruction rates (k) demonstrated that the bacterial stability was greater in tablets than in powders (kpowders>ktablets). A new mathematical model was developed combining compression and temperature parameters to predict the bacterial viability at any pressure and time. Moreover, the genetic profile of Lcr35® (Rep-PCR, microarrays), its resistance to acidity and its ability to inhibit Candidaalbicans growth, after compression, were determined to evaluate the target product profile (TPP) in a Quality by Design (QbD) approach. The Rep-PCR analysis validated the strain identity and the microarrays demonstrated the genetic stability of Lcr35® strain after compaction. Additionally, ability to inhibit the C. albicans growth was maintained and the resistance to gastric conditions of Lcr35® was even improved by tableting. As a dosage form, tablets containing probiotic can guarantee that an adequate amount of bacteria reaches the therapeutic target (intestinal or vaginal) and that the product remains stable until the time of consumption. Copyright © 2014 Elsevier B.V. All rights reserved.
Waterman, Kenneth C; Chen, Lili; Waterman, Philip; MacDonald, Bruce C; Monahan, Andrew P; Scrivens, Garry
A model is presented for determining the time when an active pharmaceutical ingredient in tablets/powders will remain within its specification limits during an in-use period; that is, when a heat-induction sealed bottle is opened for fixed time periods and where tablets are removed at fixed time points. This model combines the Accelerated Stability Assessment Program to determine the impact on degradation rates of relative humidity (RH) with calculations of the RH as a function of time for the dosage forms under in-use conditions. These calculations, in a conservative approach, assume that the air inside bottles with broached heat-induction seals completely exchanges with the external environment during periods when the bottle remains open. The solid dosages are assumed to sorb water at estimable rates during these openings. When bottles are capped, the moisture vapor transmission rate can be estimated to determine the changing RH inside the bottles between opening events. The impact of silica gel desiccants can also be included in the modeling.
Edelman, Gerda; Lopatka, Martin; Aalders, Maurice
The general procedure followed in the examination of ecstasy tablets for profiling purposes includes a color description, which depends highly on the observers' perception. This study aims to provide objective quantitative color information using visible hyperspectral imaging. Both self-manufactured and illicit tablets, created with different amounts of known colorants were analyzed. We derived reflectance spectra from hyperspectral images of these tablets, and successfully determined the most likely colorant used in the production of all self-manufactured tablets and four of five illicit tablets studied. Upon classification, the concentration of the colorant was estimated using a photon propagation model and a single reference measurement of a tablet of known concentration. The estimated concentrations showed a high correlation with the actual values (R(2) = 0.9374). The achieved color information, combined with other physical and chemical characteristics, can provide a powerful tool for the comparison of tablet seizures, which may reveal their origin. © 2013 American Academy of Forensic Sciences.
Muñoz, H; Castan, H; Clares, B; Ruiz, M A
Fast dissolving disintegrating tablets (FDDTs) containing different dosages of melatonin have been manufactured for administration to a specific target population: pediatric patients, having potential difficulties taking other oral forms. The lower dosages (3 and 5mg) are intended for epileptic children, migraine prevention, neurodevelopmental disability, sleep disorders and blindness. Dosages of 10 and 60 mg are intended for Duchenne muscular dystrophy. Two FDDT groups have been designed, one which has excipients for direct compression and others having direct compression and effervescent excipients. Tablets have been produced having disintegration times of less than 25s and with friability and hardness values that require no special storage or packaging conditions. Copyright © 2014. Published by Elsevier B.V.
Paltauf, F; Pristautz, H; el Eisch, I A
The absorption, blood level and renal excretion of chlorphenoxyisobutyric acid (clofibric acid) were examined following oral dosage of the magnesium salt (magnesium clofibrate) in a combination preparation containing meso-inositol hexanicotinate. Absorption of clofibric acid was found to be identical with that obtained with ethyl-alpha-p-chlorphenoxyisobutyrate (Clofibrate) reaching almost 100%. After dosage with the combination preparation, the maximum blood level of clofibric acid was achieved after 2 hours, in contrast to 4 hours for Clofibrate. No accumulation of clofibric acid in the blood was found after 60 days treatment with combination preparation at a daily dosage of 3 tablets. Urinary excretion of clofibric acid for both the combination drug and Clofibrate was 90% in 48 hours.
Fang, Ching; Liu, Ju-Tsung; Lin, Cheng-Huang
This work describes a novel method for the accurate determination of lysergic acid diethylamide (LSD) in tablets. A technique involving sweeping-micellar electrokinetic chromatography (MEKC) was used for the initial on-line concentration and separation, after which a cryogenic molecular fluorescence experiment was performed at 77 K. Using this approach, not only the separation of LSD from the tablet extract was achieved, but on-line spectra were readily distinguishable and could be unambiguously assigned. The results are in agreement with analyses by gas chromatography-mass spectrometry (GC-MS). Thus, this method, which was found to be accurate, sensitive and rapid, has the potential for use as a reliable complementary method to GC-MS in such analyses.
Doreth, Maria; Hussein, Murtadha Abdul; Priemel, Petra A; Grohganz, Holger; Holm, René; Lopez de Diego, Heidi; Rades, Thomas; Löbmann, Korbinian
In situ amorphization is a concept that allows to amorphize a given drug in its final dosage form right before administration. Hence, this approach can potentially be used to circumvent recrystallization issues that other amorphous formulation approaches are facing during storage. In this study, the feasibility of microwave irradiation to prepare amorphous solid dispersions (glass solutions) in situ was investigated. Indomethacin (IND) and polyvinylpyrrolidone K12 (PVP) were tableted at a 1:2 (w/w) ratio. In order to study the influence of moisture content and energy input on the degree of amorphization, tablet formulations were stored at different relative humidity (32, 43 and 54% RH) and subsequently microwaved using nine different power-time combinations up to a maximum energy input of 90kJ. XRPD results showed that up to 80% (w/w) of IND could be amorphized within the tablet. mDSC measurements revealed that with increasing microwaving power and time, the fractions of crystalline IND and amorphous PVP reduced, whereas the amount of in situ formed IND-PVP glass solution increased. Intrinsic dissolution showed that the dissolution rate of the microwaved solid dispersion was similar to that of a quench cooled, fully amorphous glass solution even though the microwaved samples contained residual crystalline IND. Copyright © 2017 Elsevier B.V. All rights reserved.
Jiang, Tao; Li, Hui-Shan; Han, Geon Goo; Singh, Bijay; Kang, Sang-Kee; Bok, Jin-Duck; Kim, Dae-Duk; Hong, Zhong-Shan; Choi, Yun-Jaie; Cho, Chong-Su
As alternatives to antibiotics in livestocks, probiotics have been used, although most of them in the form of liquid or semisolid formulations, which show low cell viability after oral administration. Therefore, suitable dry dosage forms should be developed for livestocks to protect probiotics against the low pH in the stomach such that the products have higher probiotics survivability. Here, in order to develop a dry dosage forms of probiotics for poultry, we used hydroxypropyl methylcellulose phthalate 55 (HPMCP 55) as a tablet-forming matrix to develop probiotics in a tablet form for poultry. Here, we made three different kinds of probiotics-loaded tablet under different compression forces and investigated their characteristics based on their survivability, morphology, disintegration time, and kinetics in simulated gastrointestinal fluid. The results indicated that the probiotics formulated in the tablets displayed higher survival rates in acidic gastric conditions than probiotics in solution. Rapid release of the probiotics from the tablets occurred in simulated intestinal fluid because of fast swelling of the tablets in neutral pH. As a matrix of tablet, HPMCP 55 provided good viability of probiotics after 6 months under refrigeration. Moreover, after oral administration of probiotics-loaded tablets to chicken, more viable probiotics were observed, than with solution type, through several digestive areas of chicken by the tablets.
Harrison, P C; Mainolfi, E; Madwed, J B
Intercellular adhesion molecule-1 (ICAM-1) is believed to play a role in acute rejection of allografted tissues. This molecule is involved in the interaction of T cells with antigen-presenting cells expressed on the vascular endothelium of transplanted organs and is involved in the adhesion of inflammatory cells to this endothelium and their subsequent migration into the underlying tissues. Rat abdominal heterotopic heart transplantation was used to study the role of ICAM-1 in the rejection process. American Cancer Institute rats were used as donors; Lewis rats were used as recipients. Graft survival was monitored daily via donor heart palpation. Nine groups (n = 6/group) were studied: untreated controls; olive oil; cyclosporine at 1.5, 2.75, and 5.0 mg/kg, respectively; R3.1, a control monoclonal antibody; 1A29, a rat anti-ICAM-1 monoclonal antibody, 3 mg/kg administered intraperitoneally; a combination of 1A29 (3 mg/kg) and cyclosporine (1.5 mg/kg); and a combination of 1A29 (3 mg/kg) and cyclosporine (2.75 mg/kg). Mean rejection time was 8.8 +/- 0.6 days for the untreated allografted controls and 9.7 +/- 1.1 days for the olive oil controls. Cyclosporine (1.5, 2.75, and 5.0 mg/kg) showed mean rejection times of 8.5 +/- 0.3, 20.5 +/- 1.9, and 28.8 +/- 3.6 days, respectively. The 1A29 treatment showed a mean rejection time of 9.3 +/- 0.7 days. Combination therapy of 1A29 and cyclosporine at 1.5 or 2.75 mg/kg demonstrated mean rejection times of 17.7 +/- 3.3 and 29.2 +/- 6.7 days, respectively. Thus 1A29 alone does not prolong cardiac allograft survival; however, combination therapy with either a subthreshold or a moderate dose of cyclosporine significantly extends the time to rejection of heterotopically transplanted rat hearts. Although monotherapy with an ICAM-1 antagonist alone may not be beneficial in preventing acute rejection episodes after organ transplantation, combination therapy of an anti-ICAM-1 monoclonal antibody may allow for a reduction in the dose
Yang, Yong-Ge; Song, Li-Xue; Jiang, Nan; Xu, Xue-Ting; Di, Xiao-Hui; Zhang, Mei
Objective: To investigate the pharmacokinetics of Ambroxol and Clenbuterol Tablets in Chinese healthy volunteers after a single or multiple dosages oral administration. Methods: A total of 9 healthy adult subjects were given Ambroxol and Clenbuterol Tablets in a single dosage or multiple dosages respectively. LC/MS/MS were used for the determination of Ambroxol and Clenbuterol of in plasma. The important pharmacokinetic parameters were calculated by DAS 2.0 software (compartment model). Results: Single and multiple dosage groups of Ambroxol and Clenbuterol were all fitted two-compartment model. The pharmacokinetics fitted first order kinetics process. No difference in pharmacokinetics of Ambroxol in single and multiple dosage groups volunteers was observed, Which showed no marked changes, suggesting that multiple dosing did not influence the velocity of drug metabolism. Moreover, parameters of Clenbuterol had significant difference between the single and multiple dosage groups (PAmbroxol after repeated dosing. But obvious accumulation of Clenbuterol was noted in multiple-dose administration. The established method is sensitive, accurate, reliable and specific, and it can meet the requirement of clinical pharmacokinetic trial. PMID:26770490
Järvinen, Maiju A; Paaso, Janne; Paavola, Marko; Leiviskä, Kauko; Juuti, Mikko; Muzzio, Fernando; Järvinen, Kristiina
Continuous processing is becoming popular in the pharmaceutical industry for its cost and quality advantages. This study evaluated the mechanical properties, uniformity of dosage units and drug release from the tablets prepared by continuous direct compression process. The tablet formulations consisted of acetaminophen (3-30% (w/w)) pre-blended with 0.25% (w/w) colloidal silicon dioxide, microcrystalline cellulose (69-96% (w/w)) and magnesium stearate (1% (w/w)). The continuous tableting line consisted of three loss-in-weight feeders and a convective continuous mixer and a rotary tablet press. The process continued for 8 min and steady state was reached within 5 min. The effects of acetaminophen content, impeller rotation rate (39-254 rpm) and total feed rate (15 and 20 kg/h) on tablet properties were examined. All the tablets complied with the friability requirements of European Pharmacopoeia and rapidly released acetaminophen. However, the relative standard deviation of acetaminophen content (10% (w/w)) increased with an increase in impeller rotation rate at a constant total feed rate (20 kg/h). A compression force of 12 kN tended to result in greater tablet hardness and subsequently a slower initial acetaminophen release from tablets when compared with those made with the compression force of about 8 kN. In conclusion, tablets could be successfully prepared by a continuous direct compression process and process conditions affected to some extent tablet properties.
Markl, Daniel; Wahl, Patrick; Pichler, Heinz; Sacher, Stephan; Khinast, Johannes G
This study demonstrates the use of optical coherence tomography (OCT) to simultaneously characterize the roughness of the tablet core and coating of pharmaceutical tablets. OCT is a high resolution non-destructive and contactless imaging methodology to characterize structural properties of solid dosage forms. Besides measuring the coating thickness, it also facilitates the analysis of the tablet core and coating roughness. An automated data evaluation algorithm extracts information about coating thickness, as well as tablet core and coating roughness. Samples removed periodically from a pan coating process were investigated, on the basis of thickness and profile maps of the tablet core and coating computed from about 480,000 depth measurements (i.e., 3D data) per sample. This data enables the calculation of the root mean square deviation, the skewness and the kurtosis of the assessed profiles. Analyzing these roughness parameters revealed that, for the given coating formulation, small valleys in the tablet core are filled with coating, whereas coarse features of the tablet core are still visible on the final film-coated tablet. Moreover, the impact of the tablet core roughness on the coating thickness is analyzed by correlating the tablet core profile and the coating thickness map. The presented measurement method and processing could be in the future transferred to in-line OCT measurements, to investigate core and coating roughness during the production of film-coated tablets. Copyright © 2017. Published by Elsevier B.V.
Belladonna alkaloid combinations and phenobarbital are used to relieve cramping pains in conditions such as irritable bowel syndrome and ... Belladonna alkaloid combinations and phenobarbital come as a regular tablet, a slow-acting tablet, capsule, and liquid to take ...
Full Text Available The present paper describes the development of quick stability indicating RP-HPLC method for the simultaneous estimation of codeine phosphate and chlorpheniramine maleate in the presence of its degradation products, generated from forced degradation studies. The developed method separates codeine phosphate and chlorpheniramine maleate in impurities/degradation products. Codeine phosphate and chlorpheniramine maleate and their combination drug product were exposed to acid, base, oxidation, dry heat, and photolytic stress conditions, and the stressed samples were analysed by proposed method. The proposed HPLC method utilizes the Shimadzu HPLC system on a Phenomenex C18 column (, 5 μ using a mixture of 1% o-phosphoric acid in water : acetonitrile : methanol (78 : 10 : 12 mobile phase with pH adjusted to 3.0 in an isocratic elution mode at a flow rate of 1 mL/min, at 23°C with a load of 20 μL. The detection was carried out at 254 nm. The retention time of codeine phosphate and chlorpheniramine maleate was found to be around 3.47 min and 9.45 min, respectively. The method has been validated with respect to linearity, robustness, precision, accuracy, limit of detection (LOD, and limit of quantification (LOQ. The developed validated stability indicating HPLC method was found to be simple, accurate, and reproducible for the determination of instability of these drugs in bulk and commercial products.
compartmental analy- sis. The parameters for the uncoated ..... Drug absorption' from the uncoated tablets was fast and occurred _ over a relatively short period of time 'whilst ab- sorption from the ﬁlm-coated tablets was slow and occurred over an extended ...
Remmelgas, Johan; Simonutti, Anne-Laure; Ronkvist, Asa; Gradinarsky, Lubomir; Löfgren, Anders
A mechanistic model for the prediction of in-use moisture uptake of solid dosage forms in bottles is developed. The model considers moisture transport into the bottle and moisture uptake by the dosage form both when the bottle is closed and when it is open. Experiments are carried out by placing tablets and desiccant canisters in bottles and monitoring their moisture content. Each bottle is opened once a day to remove one tablet or desiccant canister. Opening the bottle to remove a tablet or canister also causes some exchange of air between the bottle headspace and the environment. In order to ascertain how this air exchange might depend on the customer, tablets and desiccant canisters are removed from the bottles by either carefully removing only one or by pouring all of the tablets or desiccant canisters out of the bottle, removing one, and pouring the remaining ones back into the bottle. The predictions of the model are found to be in good agreement with experimental data for moisture sorption by desiccant canisters. Moreover, it is found experimentally that the manner in which the tablets or desiccant canisters were removed does not appreciably affect their moisture content. Copyright © 2012 Elsevier B.V. All rights reserved.
Carrillo, Antonio; Cejudo, José Manuel; Domínguez, Fernando; Rodríguez, Eduardo
Graphics tablet technology is well known in markets such as manufacturing, graphics arts and design but it has not yet found widespread acceptance for university teaching. A graphics tablet is an affordable teaching tool that combines the best features from traditional and new media. It allows developing a progressive, interactive lecture (as a…
Purpose: To develop bioadhesive tablets of diltiazem hydrochloride with a unique combination of bioadhesion and drug release. Method: Tablets were prepared by physical blending of diltiazem hydrochloride with two polymers, viz., carbopol and hydroxylpropyl methyl cellulose in different ratio along with other excipients.
Learn all you need to know about your Android tablet in one quick and easy reference! It's not a computer and it's not a smartphone-so what in the world is it? Whether you're new to Android or new to tablets altogether, you're about to experience mobile computing like never before with this fun, full-color guide! Inside, longtime and bestselling author Dan Gookin walks you through setting up your Android tablet, navigating the interface, browsing the web, setting up email, connecting to social media, finding plenty of apps, music, books, and movies to indulge your interests-and so much more.
Davis, Eric; Cheung, Ken; Pauls, Steve; Dick, Jonathan; Roth, Elijah; Zalewski, Nicole; Veldhuizen, Christopher; Coeler, Joel
In this laboratory experiment, lower- and upper-division students dissolved bismuth subsalicylate tablets in acid and precipitated the resultant Bi[superscript 3+] in solution with sodium phosphate for a gravimetric determination of bismuth subsalicylate in the tablets. With a labeled concentration of 262 mg/tablet, the combined data from three…
Allesø, Morten; Carstensen, Jens Michael; Holm, Per
deformation of the microcrystalline cellulose resulted in a smoother tablet surface. This altogether demonstrated that the technique provides the pharmaceutical developer with a reliable, quantitative response parameter for visual appearance of solid dosage forms, which may be used for process and ultimately...... milliseconds) and quantitatively measure the obtained surface topography of the produced tablets. Compaction history, in the form of applied roll force and tablet punch pressure, was also reflected in the measured smoothness of the tablet surfaces. Generally it was found that a higher degree of plastic...
This book presents guidelines for a future device type: a tablet that allows ergonomic front- and back-of-device interaction. These guidelines help designers and developers of user interfaces to build ergonomic applications for tablet devices, in particular for devices that enable back-of-device interaction. In addition, manufacturers of tablet devices obtain arguments that back-of-device interaction is a promising extension of the interaction design space and results in increased input capabilities, enriched design possibilities, and proven usability. The guidelines are derived from empirical studies and developed to fit the users’ skills to the way the novel device type is held. Three particular research areas that are relevant to develop design guidelines for tablet interaction are investigated: ergonomic gestures, interaction areas, and pointing techniques.
M. E. Kim
Full Text Available Interest to research in the development of new formulations of antituberculosis drugs due to the high incidence of tuberculosis in the Republic of Kazakhstan and the Russian Federation nowadays, including with acquired drug resistance. The reason for the development of acquired drug resistance is to interrupt the treatment of patients is the high toxicity of antituberculosis drugs. The improving the efficiency of antituberculosis therapy remains one of the most pressing.The aim this study was to review the dosage forms of antituberculosis drugs currently used and the ways to improve them.Methods. The study was conducted on the basis of scientific analysis (eLibrary database, PubMed, Cyberleninca, patent (kzpatents, reference (Klifar, Drugs register and technical literature.Results. It was revealed that the antituberculosis drugs are available in the form of tablets, capsules, granules for oral use and injection solutions. The advantages and disadvantages of oral dosage forms of antituberculosis drugs: tablets, capsules, granules, syrups, suspensions are described. The importance of the development and implementation in practice of pediatric formulations of antituberculosis drugs is mentioned. The state of current research inhaled formulations for the treatment of tuberculosis is described. The prospects of directional inhalation exposure by immobilization of antituberculosis drugs in liposomes, niosomes, nanocapsules, micelles, micro- and nanoparticles are mentioned. The prospect of the rectal formulations use is described. The increase in interest in the molecular encapsulation of medicinal substances with cyclodextrins in connection with the possibility of increasing the bioavailability of active ingredients, reduce the harmful effects on the gastrointestinal tract, extension, elimination of interaction of incompatible components in combination preparations, the protection of unstable substances is
Etti, C J; Yusof, Y A; Chin, N L; Mohd Tahir, S
The tableting properties of Labisia pumila herbal powder, which is well known for its therapeutic benefits was investigated. The herbal powder was compressed into tablets using a stainless steel cylindrical uniaxial die of 13-mm- diameter with compaction pressures ranging from 7 to 25 MPa. Two feed weights, 0.5 and 1.0 g were used to form tablets. Some empirical models were used to describe the compressibility behavior of Labisia pumila tablets. The strength and density of tablets increased with increase in compaction pressure and resulted in reduction in porosity of the tablets. Smaller feeds, higher forces and increase in compaction pressure, contributed to more coherent tablets. These findings can be used to enhance the approach and understanding of tableting properties of Labisia pumila herbal powder tablets.
Moës, A J
This article begins with a review of gastric emptying, small intestine transit, and colonic transit of drug delivery systems with special attention paid to the different physiological processes involved in stomach emptying and to the cut-off size of nondigestible solids for passage through the gastroduodenal junction during the digestive phase. Then, the proposed means for prolonging the gastric residence time (GRT) of drug delivery systems are reviewed and analyzed with special emphasis on floating (F) dosage forms. The following means are discussed: the use of passage-delaying agents, large single-unit dosage forms, bioadhesive drug delivery systems, "heavy" pellets, and buoyant forms. In the section devoted to bioadhesive forms, the influence of the turnover time of the intestinal mucus gel layer on the performance of mucoadhesive preparations is pointed out to explain the poor results obtained in humans with such peroral products. The use of a specifically designed apparatus for measuring the total force acting vertically on an object immersed in a liquid is presented as a methodology for selecting optimized buoyant formations in vitro. Scintigraphic studies are described in nonfasting human volunteers either in upright or in supine posture, who concurrently were given one optimized F and one nonfloating (NF) hydrophilic matrix capsules of the same size, for three different sizes (small, medium, and large). In upright subjects, the F forms stayed continuously above the gastric contents irrespective of their size, whereas the NF ones sank rapidly after administration and never rose back to the surface thereafter. Consequently, the F forms show prolonged and more reproducible GRTs compared to the NF ones. The significance and extent of this prolongation are the most marked for the small size units (p 0.05). Moreover, there is no significant difference between the mean GRTs of the small, medium, and large F units (p > 0.05). This indirectly confirms that the
Lim, Young-Suk; Ahn, Sang Hoon; Lee, Kwan Sik; Paik, Seung Woon; Lee, Youn-Jae; Jeong, Sook-Hyang; Kim, Ju-Hyun; Yoon, Seung Kew; Yim, Hyung Joon; Tak, Won Young; Han, Sang-Young; Yang, Jenny C; Mo, Hongmei; Garrison, Kimberly L; Gao, Bing; Knox, Steven J; Pang, Phillip S; Kim, Yoon Jun; Byun, Kwan-Soo; Kim, Young Seok; Heo, Jeong; Han, Kwang-Hyub
The standard-of-care regimen for chronic hepatitis C virus (HCV) infection in Korea, pegylated-interferon-alpha plus ribavirin, is poorly tolerated. Ledipasvir/sofosbuvir is a two-drug, fixed-dose combination tablet approved in the USA, European Union, and Japan for chronic genotype 1 HCV infection. This single-arm, phase IIIb study (NCT02021656) investigated the efficacy and safety of ledipasvir/sofosbuvir fixed-dose combination tablet for 12 weeks in treatment-naïve and treatment-experienced Korean patients chronically infected with genotype 1 HCV with or without compensated cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 99 % (92/93), with rates of 100 % (46/46) and 98 % (46/47) in treatment-naïve and treatment-experienced patients, respectively. There were no on-treatment failures. One patient relapsed after the end of treatment. The most common treatment-emergent adverse events were headache (8 %, 7/93) and fatigue (6 %, 6/93). There were no grade 3 or 4 adverse events, seven grade 3 laboratory abnormalities, and one premature discontinuation of study treatment (due to nonserious mouth ulceration). None of the three reported serious adverse events were related to treatment. These data suggest that 12 weeks of ledipasvir/sofosbuvir is effective and well tolerated in treatment-naïve and treatment-experienced Korean patients with chronic genotype 1 HCV infection.
ALI AL KAF
Full Text Available Two simple, rapid, and extractive spectrophotometric methods were developed for the determination of tadalafil (TDF in both pure and tablet dosage form. These methods are based on the formation of ion-pair complexes between the basic nitrogen of the drug with bromocresol purple (BCP and methyl orange (MO in acidic buffer solution. The formed complexes were extracted with chloroform and measured at 410 and 425 nm using BCP and MO, respectively. Beer’s law was obeyed in the range 2.0–20 μg mL−1 with correlation coefficient (n = 6 ≥0.9996. The molar absorptivity, Sandell sensitivity, detection and quantification limits were also calculated. The composition of the ion pairs was found 1:1 by Job’s method. The proposed methods have been applied successfully for the analysis of TDF in pure and in its dosage forms. These developed methods were validated for accuracy and precision.
Full Text Available Purpose: The aim of this study was to design, formulate and physicochemically evaluate effervescent ranitidine hydrochloride (HCl tablets since they are easily administered while the elderly and children sometimes have difficulties in swallowing oral dosage forms. Methods: Effervescent ranitidine HCl tablets were prepared in a dosage of 300 mg by fusion and direct compression methods. The powder blend and granule mixture were evaluated for various pre-compression characteristics, such as angle of repose, compressibility index, mean particle size and Hausner's ratio. The tablets were evaluated for post-compression features including weight variation, hardness, friability, drug content, dissolution time, carbon dioxide content, effervescence time, pH, content uniformity and water content. Effervescent systems with appropriate pre and post-compression qualities dissolved rapidly in water were selected as the best formulations. Results: The results showed that the flowability of fusion method is more than that of direct compression and the F5 and F6 formulations of 300 mg tablets were selected as the best formulations because of their physicochemical characteristics. Conclusion: In this study, citric acid, sodium bicarbonate and sweeteners (including mannitol, sucrose and aspartame were selected. Aspartame, mint and orange flavors were more effective for masking the bitter taste of ranitidine. The fusion method is the best alternative in terms of physicochemical and physical properties.
Aslani, Abolfazl; Jahangiri, Hajar
The aim of this study was to design, formulate and physicochemically evaluate effervescent ranitidine hydrochloride (HCl) tablets since they are easily administered while the elderly and children sometimes have difficulties in swallowing oral dosage forms. Effervescent ranitidine HCl tablets were prepared in a dosage of 300 mg by fusion and direct compression methods. The powder blend and granule mixture were evaluated for various pre-compression characteristics, such as angle of repose, compressibility index, mean particle size and Hausner's ratio. The tablets were evaluated for post-compression features including weight variation, hardness, friability, drug content, dissolution time, carbon dioxide content, effervescence time, pH, content uniformity and water content. Effervescent systems with appropriate pre and post-compression qualities dissolved rapidly in water were selected as the best formulations. The results showed that the flowability of fusion method is more than that of direct compression and the F5 and F6 formulations of 300 mg tablets were selected as the best formulations because of their physicochemical characteristics. In this study, citric acid, sodium bicarbonate and sweeteners (including mannitol, sucrose and aspartame) were selected. Aspartame, mint and orange flavors were more effective for masking the bitter taste of ranitidine. The fusion method is the best alternative in terms of physicochemical and physical properties.
Full Text Available Sustained and controlled pellets are considered as one of the ideal dosage forms. Due to the large coverage area of pellets, loaded drugs can be absorbed completely in the body and bioavailability is improved correspondingly. Coated pellets-containing tablet is a special oral formulation consisting of various pellets with different release rate. Desired rate of drug release rate can be achieved by adjusting the proportion of pellets. However, this formulation faces strict requirements in the process of preparation. Several factors will influence release behavior of tablets, including pellet cores, coating, and tabletting. Therefore, these factors will be investigated sufficiently in this review to provide valuable information for manufacturing process.
Tan, Xueying; Hu, Jingbo
Sustained and controlled pellets are considered as one of the ideal dosage forms. Due to the large coverage area of pellets, loaded drugs can be absorbed completely in the body and bioavailability is improved correspondingly. Coated pellets-containing tablet is a special oral formulation consisting of various pellets with different release rate. Desired rate of drug release rate can be achieved by adjusting the proportion of pellets. However, this formulation faces strict requirements in the process of preparation. Several factors will influence release behavior of tablets, including pellet cores, coating, and tabletting. Therefore, these factors will be investigated sufficiently in this review to provide valuable information for manufacturing process.
combined effect of two formulation variables - amounts of microcrystalline cellulose and mannitol. Results: The results of multiple regression analysis revealed that in order to obtain a fast dissolving tablet of the Aloe vera gel, an optimum concentration of mannitol and a higher content of microcrystalline cellulose should be ...
Getyala, Anil; Gangadharappa, H V; Prasad, M Sarat Chandra; Reddy, M Praveen Kumar; Kumar, T M Pramod
The aim of the work is to modify the solubility and bioavailability of Losartan potassium, by employing noneffervescent floating drug delivery (tablet dosage forms). Non-effervescent systems are a type of floating drug delivery systems, that have been used to boost the gastric residence and the floatation time in the gastro intestinal tract. The study included formulation of floating tablets using polymers like Chitosan and Karaya gum as matrix forming agents. Accurel(®) MP 1000 was used as floating agent. The tablets were prepared by direct compression technique. FTIR, DSC studies conformed that there was no incompatibility between the polymer and the drug. Tablet preformulation parameters were within the Pharmacopoeial limit. Tablet showed zero lag time, contisnuance of buoyancy for >12 h. The tablet showed good in vitro release. Drug release was through swelling and abided by the gellation mechanism. In vivo X-ray studies depicted that tablets continued to float in the GIT for 12 h. Accelerated stability showed that, tablets were stable for over 6 month. Thus the prepared non-effervescent floating tablet of Losartan potassium can be used for the treatment of hypertension for more than 12 h with single dose administration.
Tomita, Takashi; Goto, Hidekazu; Yoshimura, Yuya; Tsubouchi, Yoshiko; Nakanishi, Rie; Kojima, Chikako; Yoneshima, Mihoko; Yoshida, Tadashi; Tanaka, Katsuya; Sumiya, Kenji; Kohda, Yukinao
It has been reported that magnesium oxide tablets are excreted in a non-disintegrated state in the stool of patients when the tablets are administered after being immersed in a food thickener. Therefore we examined whether immersion in a food thickener affects the pharmacological effect in patients taking magnesium oxide tablets, and whether immersion affects its disintegration and solubility. The mean dosage (1705 mg/d) was higher for patients who took tablets after immersion in a food thickener than for those who took non-immersed tablets (1380 mg/d). The disintegration time and dissolution rate of the immersed tablets were lower than those of non-immersed tablets in vitro. Furthermore, components that constitute the food thickener and differences in composition concentrations differentially affect the disintegration and solubility of magnesium oxide tablets. This suggests that commercially available food thickeners are likely to be associated with changes in the degradation of magnesium oxide tablets, and they therefore should be carefully used in certain clinical situations.
Dave, Vivek; Yadav, Sachdev; Sharma, Swapnil; Vishwakarma, Pushpendra; Ali, Nasir
Fast disintegrating tablets (FDTs) have received ever increasing demand during the last decade, and the ﬁeld has become a hastily growing area in the pharmaceutical industry. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. Aceclofenac, an NSAID, has been recommended orally for the treatment of bone and connective tissue disorder and thus the formulation of the same resulted in development of several FDT technologies. The present aim is to formulate a tablet which disintegrate and dissolve rapidly and give its rapid onset of action: analgesic, antipyretic and anti-inflammatory action. Besides, the conventional tablets also show poor patient compliance an attempt had been made to formulate for FDT of aceclofenac by using various super disintegrants like sodium starch glycolate, croscarmellose sodium and crosspovidone (polyplasdone XL) and PEG 6000 followed by novel technique. The tablets were evaluated for friability, hardness, weight variation, disintegration time, wetting time, in vitro dissolution studies and drug content studies. It was concluded that the batch which was prepared by using combination of crosspovidone and sodium starch glycolate as a super disintegrant shows excellent disintegration time, enhance dissolution rate, taste masking and hence lead to improve efficacy and bioavailability of drug.
Walash, M; Sharaf El-Din, M; El-Enany, Nahed; Eid, M; Shalan, Sh
A rapid, simple and highly sensitive first derivative synchronous fluorometric method has been developed for the simultaneous analysis of binary mixture of sulpiride (SUL) and mebeverine hydrochloride (MEB). The method is based upon measurement of the synchronous fluorescence intensity of these drugs at ∆λ = 100 nm in water. The different experimental parameters affecting the fluorescence of the two drugs were carefully studied and optimized. The fluorescence-concentration plots were rectilinear over the range of 0.05-1 µg/mL and 0.2-3.2 µg/mL for SUL and MEB respectively with lower detection limits (LOD) of 0.006 and 0.01 µg/mL and quantification limits (LOQ) of 0.0.02 and 0.05 µg/mL for SUL and MEB, respectively. The proposed method was successfully applied for the determination of the two compounds in synthetic mixtures and in commercial tablets. The high sensitivity attained by the proposed method allowed the determination of both of SUL and MEB metabolite (veratic acid) in real human plasma samples applying second derivative synchronous fluorometric technique. The mean% recoveries (n = 3) for both MEB metabolite (veratic acid) and SUL were 99.82 ± 2.53 and 98.84 ± 6.20 for spiked human plasma respectively, while for real human plasma, the mean% recoveries (n = 3) were 91.49 ± 4.25 and 91.36 ± 8.46 respectively.
Siiriä, Simo Matti; Antikainen, Osmo; Heinämäki, Jyrki; Yliruusi, Jouko
This study presents a new approach to model powder compression during tableting. The purpose of this study is to introduce a new discrete element simulation model for particle–particle bond formation during tablet compression. This model served as the basis for calculating tablet strength distribution during a compression cycle. Simulated results were compared with real tablets compressed from microcrystalline cellulose/theophylline pellets with various compression forces. Simulated and exper...
Full Text Available Lubrication plays a key role in successful manufacturing of pharmaceutical solid dosage forms; lubricants are essential ingredients in robust formulations to achieve this. Although many failures in pharmaceutical manufacturing operations are caused by issues related to lubrication, in general, lubricants do not gain adequate attention in the development of pharmaceutical formulations. In this paper, the fundamental background on lubrication is introduced, in which the relationships between lubrication and friction/adhesion forces are discussed. Then, the application of lubrication in the development of pharmaceutical products and manufacturing processes is discussed with an emphasis on magnesium stearate. In particular, the effect of its hydration state (anhydrate, monohydrate, dihydrate, and trihydrate and its powder characteristics on lubrication efficiency, as well as product and process performance is summarized. In addition, the impact of lubrication on the dynamics of compaction/compression processes and on the mechanical properties of compacts/tablets is presented. Furthermore, the online monitoring of magnesium stearate in a blending process is briefly mentioned. Finally, the chemical compatibility of active pharmaceutical ingredient (API with magnesium stearate and its reactive impurities is reviewed with examples from the literature illustrating the various reaction mechanisms involved.
Full Text Available Two simple, rapid and reproducible simultaneous equation and Q-Analysis UV-Spectrophotometric methods have been developed for simultaneous estimation of Etodolac (ETO and Thiocolchicoside (THC in combined tablet dosage form. The methods involved solving simultaneous equations and Q-value Analysis based on measurement of absorbance at wavelengths, 223 (λmax of ETO, 259.4 nm (λmax of THC and 236 nm (Iso-absorptive point. Linearity was found in the concentration range of 1-6 μg/mL and 4 - 24 μg/mL for ETO & THC respectively with coefficient correlation 0.9998 & 0.9992. The amount of drugs estimated by proposed methods are in excellent agreement with label claimed. Further-more, the methods were applied for the determination of ETO and THC in spiked human urine. The degradation behavior of ETO and THC was investigated under acid hydrolysis, alkali hydrolysis, photo and oxidative degradation. The samples subsequently generated were used for degradation studies using the developed method. Thiocolchicoside was found to degrade extensively under alkali hydrolysis and unaffected by other stress conditions while ETO was found to be stable in all stress conditions. The methods were validated according to ICH guidelines. The method, suitable for routine quality control, has been successfully applied to the determination of both drugs in commercial brands of tablets.
Goodwin, Daniel J; van den Ban, Sander; Denham, Mike; Barylski, Ian
A comprehensive commercial control strategy for tablet content and content uniformity focussed on the unit operation of compression is presented and is proposed to enable real time release for these critical quality attributes. The control strategy is based on process understanding, process control through compaction force weight control on the tablet press, periodic checks of mean and individual tablet weight combined with at-line testing of tablet content by near infrared (NIR). The application of the at-line NIR tablet content method is discussed and an acceptance criteria based on a parametric tolerance interval test (PTIT) is proposed. Sample handling limitations and spectral acquisition time for the NIR content method limit the sample size, however the chosen PTIT assures an appropriate level of batch coverage. Data are presented for ten commercial-scale batches that demonstrates the control strategy delivered the quality standard for content and content uniformity. Copyright © 2017 Elsevier B.V. All rights reserved.
Antonio Carrillo Andrés
Full Text Available Graphics tablet technology is well known in markets such as manufacturing, graphics arts and design but they have not yet found widespread acceptance for university teaching. A graphics tablet is an affordable and efficient teaching tool that combines the best features from traditional and new media. It allows developing a progressive, interactive lecture (as a traditional blackboard does. However, the tablet is more versatile, being able to integrate graphic material such as tables, graphs, colours, etc. In addition to that, lecture notes can be saved and posted on a course website. The objective of this paper is to show the usefulness of tablet technology in undergraduate engineering teaching by sharing experiences made using a graphics tablet for lecturing a second year Thermal Engineering course. Students’ feedback is definitely positive, though there are some caveats regarding technical and operative problems.
Novikova, Anna; Carstensen, Jens Michael; Zeitler, J. Axel
The applicability of off-line multispectral ultraviolet (UV) imaging in combination with multivariate data analysis was investigated to determine the coating thickness and its distribution on the tablet surface during lab scale coating. The UV imaging results were compared with the weight gain...... measured for each individual tablet and the corresponding coating thickness and its distribution measured by terahertz pulsed imaging (TPI). Three different tablet formulations were investigated, two of which contained UV active tablet cores. Three coating formulations were applied: Aquacoat® ECD (a mainly...... translucent coating) and Eudragit® NE (a turbid coating containing solid particles). It was shown that UV imaging is a fast and non-destructive method to predict individual tablet weight gain as well as coating thickness. The coating thickness distribution profiles determined by UV imaging correlated...
Šimek, Michal; Grünwaldová, Veronika; Kratochvíl, Bohumil
Rapid and correct production of generic solid dosage forms requires a large amount of analytical data and conclusions. Modern analytical techniques have a good resolution and accuracy and allow obtaining a lot of information about the original product. Scanning electron microscopy (SEM) is used for observation and assessing individual layers, core and surface of solid dosage forms. Fourier transform infrared (FTIR) spectroscopy mapping allows determining the distribution and characterization of individual components in a solid dosage form. However, the samples prepared by common way, using scalpel or tablet splitter, are not good enough. It was the reason for development of a new and better method of sample preparation, which uses microtome. Well-prepared samples analyzed by SEM and FTIR mapping allow to determine a solid dosage form formulation, excipient content and distribution of excipient and active pharmaceutical ingredient.
Osei-Yeboah, Frederick; Sun, Changquan Calvin
Poor powder tabletability is a common problem that challenges the successful development of high-quality tablet products. Using noncompressible microcrystalline cellulose beads, we demonstrate that surface coating is an effective strategy for modulating tabletability, almost at will, through judicious selection of coating material. This strategy has broad applicability as tabletability of such particles is dictated by the properties of the outermost layer coat regardless the nature of the core. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.
Full Text Available Fast disintegrating tablets (FDTs have received ever-increasing demand during the last decade, and the field has become a rapidly growing area in the pharmaceutical industry. Oral drug delivery remains the preferred route for administration of various drugs. Recent developments in the technology have prompted scientists to develop FDTs with improved patient compliance and convenience. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. The popularity and usefulness of the formulation resulted in development of several FDT technologies. FDTs are solid unit dosage forms, which disintegrate or dissolve rapidly in the mouth without chewing and water. FDTs or orally disintegrating tablets provide an advantage particularly for pediatric and geriatric populations who have difficulty in swallowing conventional tablets and capsules. This review describes various formulations and technologies developed to achieve fast dissolution/dispersion of tablets in the oral cavity. In particular, this review describes in detail FDT technologies based on lyophilization, molding, sublimation, and compaction, as well as approaches to enhancing the FDT properties, such as spray drying and use of disintegrants. In addition, taste-masking technologies, experimental measurements of disintegration times, and dissolution are also discussed.
Jacoba M Maurer
Full Text Available ColoPulse tablets are an innovative development in the field of oral dosage forms characterized by a distal ileum and colon-specific release. Previous studies in humans showed release in the ileo-colonic region, but the relationship between gastrointestinal pH and release was not experimentally proven in vivo. This information will complete the in vivo release-profile of ColoPulse tablets.Release from ColoPulse tablets was studied in 16 healthy volunteers using the dual label isotope strategy. To determine gastrointestinal pH profiles and transit times the IntelliCap system was used. A ColoPulse tablet containing 13C-urea and an uncoated, immediate release tablet containing 15N2-urea were taken simultaneously followed by a standardized breakfast after three hours. Five minutes after intake of the tablets the IntelliCap capsule was swallowed and pH was measured until excretion in the feces. Breath and urine samples were collected for isotope analysis.Full analysis could be performed in 12 subjects. Median bioavailability of 13C -urea was 82% (95% CI 74-94%, range 61-114%. The median lag time (5% release of 13C was 5:42 h (95% CI 5:18-6:18 h, range 2:36-6:36 h, There was no statistically significant difference between lag time based on isotope signal and colon arrival time (CAT based on pH (median 5:42 vs 5:31 h p = 0.903. In all subjects an intestinal pH value of 7.0 was reached before release of 13C from the ColoPulse tablet occurred.From the combined data from the IntelliCap system and the 13C -isotope signal it can be concluded that release from a ColoPulse tablet in vivo is not related to transit times but occurs in the ileo-colonic region after pH 7.0 is reached. This supports our earlier findings and confirms that the ColoPulse system is a promising delivery system for targeting the distal ileum and colon.ISRCTN Registry 18301880.
Perioli, Luana; D'Alba, Giuseppina; Pagano, Cinzia
Furosemide (FURO) is a drug labeled in class IV of the Biopharmaceutics Classification System (BCS) as it is both poor soluble and poor permeable. The aim of this work was to improve FURO biopharmaceutical properties by its formulation in a new solid oral dosage form. It consists in the realization of the composite MgAl-HTlc-FURO, obtained by FURO intercalation into the inorganic matrix hydrotalcite (MgAl-HTlc), and its successive formulation in tablets intended to be swallowed whole and to disintegrate rapidly in the stomach. These formulations were prepared by direct compression of a simple powder mixture constituted by MgAl-HTlc-FURO, a super disintegrant (Explotab, PolyplasdoneXL, PolyplasdoneXL-10, PolyplasdoneINF 10 or L-HPCLH-21) and a filler. The prepared formulations were submitted to disintegration time tests, and only those displaying the lowest disintegration time in gastric medium were submitted to in vitro release studies. Drug dissolution profiles from MgAl-HTlc-FURO tablets were compared with those containing crystalline FURO alone or physically mixed to MgAl-HTlc instead of MgAl-HTlc-FURO. The results revealed that tablets containing MgAl-HTlc-FURO give the best dissolution profile and that L-HPCLH-21 is able to promote the highest drug release in gastric medium, resulting in the most suitable super disintegrant in comparison with the other tested. Copyright © 2011 Elsevier B.V. All rights reserved.
Skaftason, Jóhannes F; Jóhannesson, Thorkell
Modern tablet compression was instituted in England in 1844 by William Brockedon (1787-1854). The first tablets made according to Brockedon´s procedures contained watersoluble salts and were most likely compressed without expedients. In USA a watershed occurred around 1887 when starch (amylum maydis) was introduced to disperse tablets in aqueous milieu in order to corroborate bioavailability of drugs in the almentary canal. About the same time great advances in tablet production were introduced by the British firm Burroughs Wellcome and Co. In Denmark on the other hand tablet production remained on low scale until after 1920. As Icelandic pharmacies and drug firms modelled themselves mostly upon Danish firms tablet production was first instituted in Iceland around 1930. The first tablet machines in Iceland were hand-driven. More efficent machines came after 1945. Around 1960 three sizeable tablet producers were in Iceland; now there is only one. Numbers of individual tablet species (generic and proprietary) on the market rose from less than 10 in 1913 to 500 in 1965, with wide variations in numbers in between. Tablets have not wiped out other medicinal forms for peroral use but most new peroral drugs have been marketed in the form of tablets during the last decades.
Franck, Jason; Abebe, Admassu; Keluskar, Rekha; Martin, Kyle; Majumdar, Antara; Kottala, Niranjan; Stamato, Howard
There has been increasing interest in fixed dose combination (FDC) therapy. Multi-layer tablets are a popular choice among various technologies to deliver FDCs. In most cases, round flat faced tooling is used in testing tablets as they have the simplest geometry. However, shaped tooling is more common for commercial products and may have an effect on bilayer tablet strength. Capsule shaped bilayer tablets, similar to a commercial image, and holders conforming to the tablet topology, were compared with similar round flat faced bilayer tablets and their corresponding holders. Bilayer tablets were subjected to an axial test device, until fracture and the quantitative breaking force value was recorded. As the second layer compression force increases, regardless of holder design, an increase in breaking force occurs as expected. This consistent trend provides insight regarding the breaking force of capsule shaped bilayer tablets. The results of this study show that at lower second layer compression forces, tablet geometry does not significantly impact the results. However, at higher compression forces, a significant difference in breaking force between tablet geometries exists. Therefore, using a test geometry close to the final commercial tablet image is recommended to have the most accurate prediction for tablet breakage.
Efficacy and safety of fixed dose combination of arterolane maleate and piperaquine phosphate dispersible tablets in paediatric patients with acute uncomplicated Plasmodium falciparum malaria: a phase II, multicentric, open-label study.
Toure, Offianan Andre; Rulisa, Stephen; Anvikar, Anupkumar R; Rao, Ballamudi S; Mishra, Pitabas; Jalali, Rajinder K; Arora, Sudershan; Roy, Arjun; Saha, Nilanjan; Iyer, Sunil S; Sharma, Pradeep; Valecha, Neena
The World Health Organization (WHO) recommends artemisinin combination therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria. The present study investigated the efficacy and safety of fixed dose combination (FDC) of arterolane maleate 37.5 mg and piperaquine phosphate (PQP) 187.5 mg dispersible tablets in paediatric patients aged 6 months to 12 years. Male and female patients aged 6 months to 12 years who were confirmed cases of P. falciparum mono-infection with fever or documented history of fever in the previous 24 h were included. The patients were administered FDC of arterolane maleate and PQP as single daily doses for three consecutive days based on their age. The primary efficacy outcome was proportion of patients with polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) on day 28. Safety was analysed based on adverse events (AE), laboratory abnormalities and abnormalities on electrocardiograph. A total of 141 eligible paediatric patients received FDC of arterolane maleate and PQP in a 42-day follow-up study. All the enrolled patients (141) were included in intention to treat (ITT) and safety analyses, and 126 patients were considered in per protocol (PP) population. The PCR-corrected ACPR on day 28 was achieved in all patients (100 %; 95 % CI 97.11-100) included in PP population. The median parasite clearance time (PCT) and fever clearance time (FCT) were 24 h (95 % CI 18.0-24.0) and 10 h (95 % CI 4.0-18.0), respectively. The most frequently reported clinical AE was vomiting. Majority of the AEs were mild to moderate in severity and resolved without sequelae. No patient was discontinued for any QTc (corrected QT interval) prolongation. No deaths or serious AEs were reported during the study. The findings from this study showed that FDC of arterolane maleate and PQP effectively cures P. falciparum malaria and attains acceptable level of cure by day 28 in paediatric patients. The efficacy and
Miller, J F; Welply, G A; Elstein, M
Stimulation of uterine activity after amniotomy has been carried out with prostaglandin E2 (PGE2) tablets in two dosage regimens and with intravenous oxytocin. Oxytocin stimulation was the most successful. The difference in success rate was most marked in nulliparous patients and those with low Bishop score. PMID:1120220
marketed oral controlled release products, only three approaches are employed including matrix, reservoir, osmotic, or ion exchange . Multi- layered tablets and technologies such as. Geomatrix® ... and/or inducing multi-drug release profiles in one dosage form ... 0.9983 and regression equation, y = 0.0076 +. 0.0635.
Moreira, Sebastian A; Liu, D Jeffery
Evaluate systemic exposure with repeated topical application of a fixed-combination topical gel product containing 1% diclofenac sodium and 3% menthol in either of 2 formulation packages relative to oral administration. In this phase 1, single-center, 4-way crossover study, healthy volunteers aged 18 - 50 years underwent consecutive 3-day treatment regimens in a randomly assigned sequence with each of 4 treatment groups: 4 g of topical 1% diclofenac + 3% menthol gel administered via an aluminum tube or roll-on device applied 4 times daily; 4 g of topical 1% diclofenac sodium gel (Voltaren Gel) applied 4 times daily; and oral diclofenac sodium tablets 50 mg 3 times daily. Treatment regimens were separated by 2-day washout periods. A total of 18 subjects enrolled and completed the study. Relative to oral administration, area under the concentration time curve from 48 to 72 hours (AUC48-72) with topical administration of 1% diclofenac + 3% menthol gel from a tube or roll-on device was 16.1% (90% CI: 12.2 - 21.1%) and 14.4% (90% CI: 11.0 - 19.0%), respectively. The diclofenac/menthol combination delivered significantly higher exposures of diclofenac compared with Voltaren Gel. A higher number of adverse events (AEs) occurred with the topical diclofenac/menthol combination (61%) vs. Voltaren Gel (22%) or oral diclofenac (6%); most were local skin reactions. No difference in systemic AEs was observed among the groups. As expected, systemic exposure was significantly lower with the topical diclofenac/menthol treatment regimens compared with oral diclofenac. Local skin AEs were increased with the topical combination product, but the risk of systemic AEs was low. .
Vynckier, A-K; Lin, H; Zeitler, J A; Willart, J-F; Bongaers, E; Voorspoels, J; Remon, J P; Vervaet, C
In this study calendering is used as a downstream technique to shape monolithic co-extruded fixed-dose combination products in a continuous way. Co-extrudates with a metoprolol tartrate-loaded sustained-release core and a hydrochlorothiazide-loaded immediate-release coat were produced and immediately shaped into a monolithic drug delivery system via calendering, using chilled rolls with tablet-shaped cavities. In vitro metoprolol tartrate release from the ethylcellulose core of the calendered tablets was prolonged in comparison with the sustained release of a multiparticulate dosage form, prepared manually by cutting co-extrudates into mini-matrices. Analysis of the dosage forms using X-ray micro-computed tomography only detected small differences between the pore structure of the core of the calendered tablet and the mini-matrices. Diffusion path length was shown to be the main mechanism behind the release kinetics. Terahertz pulsed imaging visualized that adhesion between the core and coat of the calendered tablet was not complete and a gradient in coat thickness (varying from 200 to 600μm) was observed. Modulated differential scanning calorimetry and X-ray diffraction indicated that the solid-state properties of both drugs were not affected by the calendering procedure. Copyright © 2015 Elsevier B.V. All rights reserved.
Goyanes, Alvaro; Chang, Hanah; Sedough, Daniel; Hatton, Grace B; Wang, Jie; Buanz, Asma; Gaisford, Simon; Basit, Abdul W
The aim of this work was to explore the feasibility of using fused deposition modelling (FDM) 3D printing (3DP) technology with hot melt extrusion (HME) and fluid bed coating to fabricate modified-release budesonide dosage forms. Budesonide was sucessfully loaded into polyvinyl alcohol filaments using HME. The filaments were engineered into capsule-shaped tablets (caplets) containing 9mg budesonide using a FDM 3D printer; the caplets were then overcoated with a layer of enteric polymer. The final printed formulation was tested in a dynamic dissolution bicarbonate buffer system, and two commercial budesonide products, Cortiment® (Uceris®) and Entocort®, were also investigated for comparison. Budesonide release from the Entocort® formulation was rapid in conditions of the upper small intestine while release from the Cortiment® product was more delayed and very slow. In contrast, the new 3D printed caplet formulation started to release in the mid-small intestine but release then continued in a sustained manner throughout the distal intestine and colon. This work has demonstrated the potential of combining FDM 3DP with established pharmaceutical processes, including HME and film coating, to fabricate modified release oral dosage forms. Copyright © 2015. Published by Elsevier B.V.
Expert visual guidance to getting the most out of your Fire tablet Teach Yourself VISUALLY Fire Tablets is the comprehensive guide to getting the most out of your new Fire tablet. Learn to find and read new bestsellers through the Kindle app, browse the app store to find top games, surf the web, send e-mail, shop online, and much more! With expert guidance laid out in a highly visual style, this book is perfect for those new to the Fire tablet, providing all the information you need to get the most out of your device. Abundant screenshots of the Fire tablet graphically rich, touch-based Androi
Wang, Yimin; Armenante, Piero M
Dissolution testing is routinely conducted in the pharmaceutical industry to provide in vitro drug release information for quality control purposes. The most common dissolution testing system for solid dosage forms is the United States Pharmacopeia (USP) Dissolution Testing Apparatus 2. This apparatus is very sensitive to the initial location of the tablet, which cannot be controlled because the tablet is dropped into the vessel at the beginning of the test and it may rest at random locations at the vessel's bottom. In this work, a modified Apparatus 2 in which the impeller was placed 8 mm off center in the vessel was designed and tested. This new design was termed "OPI" for "off-center paddle impeller." Dissolution tests were conducted with the OPI apparatus for nine different tablet locations using both disintegrating tablets (prednisone) and nondisintegrating tablets (salicylic acid). The dissolution profiles in the OPI apparatus were largely independent of the tablet location at the vessel's bottom, whereas those obtained in the Standard System generated statistically different profiles depending on the tablet location. The newly proposed OPI system can effectively eliminate artifacts generated by random settling of the tablet at the vessel's bottom, thus making the test more robust. Copyright © 2011 Wiley Periodicals, Inc.
During the summer of 2007 an internet hype was unleashed by the breaking news that an Old Testament name of some importance, figuring in the Book of Jeremiah Ch. 39, had been positively identified on a cuneiform clay tablet, viz. a bill of receipt from the time of this prophet's floruit. Many a
Full Text Available This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 was used to prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation variables such as content of talc (10%, 25% and 40%, plasticisers (TEC and DBS, dosage of plasticiser (10%, 20% and 30% and coating weight (2%, 3% and 5% were evaluated for drug release characteristics. The in vitro release was studied using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8 revealed that the prepared tablets were able to sustain drug release into the intestine and a first-order release was obtained for capsaicin. This research is the first report of the preparation and content determination of CCMS enteric coated tablets. The sustained release behavior of enteric coated formulations in pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery platform for sustained delivery of gastric irritant drugs.
Otsuka, Makoto; Tomita, Hisako; Otsuka, Kuniko; Kamae, Isao; Jorgenson, James A
Ibuprofen tablets on the market in Japan and the USA were compared by manual- and automatic-dissolution tests according to USP24 criteria. Dissolution test were performed in 900 ml of phosphate buffer of pH 7.2 at 37.0+/-0.5 degrees C at 50 rpm for 60 min, and the time required for 70% dissolution (T70%) and 5% dissolution after 60 min (A60) were evaluated. The dissolution profiles of both Japanese and American tablets by the automatic-method showed almost the same profiles as those of the manual method. T70% of the American and Japanese tablets by the manual method were not significantly different (p>0.05) from the automatic-method at various sampling positions. The A60 of the American and Japanese tablets by the manual-method was not significantly different (p>0.05) except at one position. The results indicate that the automatic-method was more reproducible than the manual-method, and also that systematic error was negligible. The T70% and A60 of the American tablets were significantly different (p<0.05) from the Japanese tablets. The American tablets were a film-coated over-the-counter drug and the Japanese tablets were a sugar-coated prescription drug. There was a difference in dissolution behavior between the dosage forms of the two countries.
Goyanes, Alvaro; Buanz, Asma B M; Basit, Abdul W; Gaisford, Simon
The use of fused-filament 3D printing (FF 3DP) to fabricate individual tablets is demonstrated. The technology permits the manufacture of tablets containing drug doses tailored to individual patients, or to fabrication of tablets with specific drug-release profiles. Commercially produced polyvinyl alcohol (PVA) filament was loaded with a model drug (fluorescein) by swelling of the polymer in ethanolic drug solution. A final drug-loading of 0.29% w/w was achieved. Tablets of PVA/fluorescein (10 mm diameter) were printed using a 3D printer. It was found that changing the degree of infill percentage in the printer software varied the weight and volume of the printed tablets. The tablets were mechanically strong and no significant thermal degradation of the active occurred during printing. Dissolution tests were conducted in modified Hank's buffer. The results showed release profiles were dependent on the infill percentage used to print the tablet. The study indicates that FF 3DP has the potential to offer a new solution for fabricating personalized-dose medicines or unit dosage forms with controlled-release profiles. In addition, the low cost of FDM printers means the paradigm of extemporaneous or point-of-use manufacture of personalized-dose tablets is both feasible and attainable. Copyright © 2014 Elsevier B.V. All rights reserved.
Chavez, Pierre-François; Sacré, Pierre-Yves; De Bleye, Charlotte; Netchacovitch, Lauranne; Mantanus, Jérôme; Motte, Henri; Schubert, Martin; Hubert, Philippe; Ziemons, Eric
The aim of this study was to develop Near infrared (NIR) methods to determine the active content of non-coated pharmaceutical tablets manufactured from a proportional tablet formulation. These NIR methods intend to be used for the monitoring of the active content of tablets during the tableting process. Firstly, methods were developed in transmission and reflection modes to quantify the API content of the lowest dosage strength. Secondly, these methods were fully validated for a concentration range of 70-130% of the target active content using the accuracy profile approach based on β-expectation tolerance intervals. The model using the transmission mode showed a better ability to predict the right active content compared to the reflection one. However, the ability of the reflection mode to quantify the API content in the highest dosage strength was assessed. Furthermore, the NIR method based on the transmission mode was successfully used to monitor at-line the tablet active content during the tableting process, providing better insight of the API content during the process. This improvement of control of the product quality provided by this PAT method is thoroughly compliant with the Quality by Design (QbD) concept. Finally, the transfer of the transmission model from the off-line to an on-line spectrometer was efficiently investigated. Copyright © 2015 Elsevier B.V. All rights reserved.
Monitoring and evaluating the quality consistency of Compound Bismuth Aluminate tablets by a simple quantified ratio fingerprint method combined with simultaneous determination of five compounds and correlated with antioxidant activities.
Liu, Yingchun; Liu, Zhongbo; Sun, Guoxiang; Wang, Yan; Ling, Junhong; Gao, Jiayue; Huang, Jiahao
A combination method of multi-wavelength fingerprinting and multi-component quantification by high performance liquid chromatography (HPLC) coupled with diode array detector (DAD) was developed and validated to monitor and evaluate the quality consistency of herbal medicines (HM) in the classical preparation Compound Bismuth Aluminate tablets (CBAT). The validation results demonstrated that our method met the requirements of fingerprint analysis and quantification analysis with suitable linearity, precision, accuracy, limits of detection (LOD) and limits of quantification (LOQ). In the fingerprint assessments, rather than using conventional qualitative "Similarity" as a criterion, the simple quantified ratio fingerprint method (SQRFM) was recommended, which has an important quantified fingerprint advantage over the "Similarity" approach. SQRFM qualitatively and quantitatively offers the scientific criteria for traditional Chinese medicines (TCM)/HM quality pyramid and warning gate in terms of three parameters. In order to combine the comprehensive characterization of multi-wavelength fingerprints, an integrated fingerprint assessment strategy based on information entropy was set up involving a super-information characteristic digitized parameter of fingerprints, which reveals the total entropy value and absolute information amount about the fingerprints and, thus, offers an excellent method for fingerprint integration. The correlation results between quantified fingerprints and quantitative determination of 5 marker compounds, including glycyrrhizic acid (GLY), liquiritin (LQ), isoliquiritigenin (ILG), isoliquiritin (ILQ) and isoliquiritin apioside (ILA), indicated that multi-component quantification could be replaced by quantified fingerprints. The Fenton reaction was employed to determine the antioxidant activities of CBAT samples in vitro, and they were correlated with HPLC fingerprint components using the partial least squares regression (PLSR) method. In
Validated column high-performance liquid chromatographic method for determination of aspirin and clopidogrel in combined tablets in the presence of degradation products formed under ICH-recommended stress conditions.
Kachhadia, Pankaj K; Doshi, Ashish S; Joshi, Hitendra S
The development and validation of a column high-performance liquid chromatographic assay method for the determination of aspirin and clopidogrel in tablet formulation are described. The combination formulation was subjected to International Conference on Harmonization-recommended stress conditions. Separation of the drugs from the degradation products formed under stress conditions was achieved on an octasilyl (C8) column using 0.3% orthophosphoric acid-acetonitrile (65 + 35, v/v) mobile phase. The method was validated for specificity, linearity, limits of detection and quantification, precision, accuracy, and robustness. The method was found to be specific against placebo interference and during the forced degradation. The response was linear in the concentration range of 30.0-120.0 microg/mL for aspirin and 15.0-60.0 microg/mL for clopidogrel, with a correlation coefficient of 0.9999 for both. The relative standard deviation values for intra- and interday precision were aspirin and 98.20 and 100.35% for clopidogrel. Stress testing showed degradation products that were well-separated from the parent compound, confirming the stability-indicating capacity of the method.
Obeidat, Wasfy M.; Nokhodchi, Ali; Alkhatib, Hatim
The purpose of this work was to investigate the influence of Eudragit®E100 polymer in modifying the release rates and compaction properties of water soluble model drug paracetamol from Carbopol®971P NF polymer matrix tablets prepared by direct compression. The effects of the ratio of the two polymers, the total polymeric content, and the tablets mechanical strength on paracetamol release rates were investigated. Dissolution studies were conducted using USP XX Π rotating paddle apparatus at 50...
Dey, Paramita; Maiti, Sabyasachi
The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug-delivery system as they have improved patient compliance and have some additional advantages compared to other oral formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to super disintegrants in the formulation. Thus this type of drug delivery helps a proper peroral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method of preparation is the compression method. Other special methods are molding, melt granulation, phase-transition process, sublimation, freeze-drying, spray-drying, and effervescent method. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test, and dissolution test. PMID:22096326
Stela R. de Oliveira
Full Text Available Soy isoflavones have been extensively used for menopausal symptoms and prevention of hormone-related cancer, osteoporosis and cardiovascular diseases. Commercially available forms of isoflavones include supplements, capsules and tablets. However, the non-standardization of soy isoflavones extracts and different dissolution profiles of these solid dosage forms highlight the need of additional studies on the development of well characterized pharmaceutical dosage forms of isoflavones. In this work, immediate release oral tablets of soy isoflavones were obtained and evaluated. Genistein and daidzein, were the main constituents of the dried soy extract. Preparation of the tables was accomplished in a rotary tableting machine following either a dry mixture for direct compression or wet granulation with different excipients. Powder, granules and tablets were evaluated for several parameters, including flow properties, Carr and Hausner indexes, hardness, friability, disintegration time and drug release profile. Also, a fast and validated HPLC analytical method for both genistein and daidzein was developed. Formulations containing sodium croscarmellose and sodium dodecyl sulfate resulted in better flowability as indicated by the flow rate and angle of repose, faster disintegration time and immediate release dissolution profile.
V. Ravi Krishna; Y. Madhusudhan Rao; P.Chinna Reddy; K. Sujatha
The objective of this study was to develop effective mucoadhesive buccal bilayered tablets of a drug containing bioadhesive layer and drug free backing layer, expected to release the drug in unidirection for extended period of time. Tablets of Furosemide were prepared by direct compression method using bioadhesive polymers like Carbopol 941NF, 971P, Methocel K4M, Methocel K15M and combination of NaCMC, Carbopol 971P in different ratios with backing layer of Cyanoacrylate adhesive tape. Buccal...
Plummer, Ruth; Swaisland, Helen; Leunen, Karin
formulation. METHODS: PK data were obtained in Part A using a two-treatment period crossover design; single-dose olaparib 300 mg (two 150 mg tablets) was administered in two prandial states: fasted and fed. In Part B, patients received olaparib tablets (300 mg bid) for 5 days under fasting conditions; in Part...... C, patients were allowed continued access to olaparib. Safety was assessed throughout, with data reported for Parts A and B. RESULTS: A total of 60 and 56 patients were evaluable for safety and PK analyses, respectively; 57 patients entered Part B. Rate of olaparib absorption was slower.......16)]. The point estimate and 90 % CI for the AUC0-∞ treatment ratio were within pre-defined bioequivalence limits (0.80-1.25). Adverse event data were consistent with the known safety profile of olaparib. CONCLUSIONS: Results of this study showed that a high-fat meal decreases the rate of absorption and peak...
The developed matrix tablet (75% drug loading resulted in 670 mg of weight for 500 mg dose strength and showed sustained drug release over 10 h. When compared, with conventional granulation techniques, it was observed that, under identical compression force, the tablet prepared by MG exhibited superior compactibility along with tablet hardness and optimal drug release profile. FTIR suggested nonexistence of chemical interaction between the drug and the other excipients while XRD and DSC analysis revealed the crystalline state of the drug. Furthermore, the results obtained from Raman spectroscopy proved the uniform distribution of the Metformin HCl and polymer in the final dosage form. This technology leads to the manufacture of sustained release matrix formulation with reduced tablet size of a high dose, highly water soluble drug otherwise difficult to process using standard batch-granulation.
Bloch, B; Smyth, E
Metronidazole tablets, benzoyl metronidazole suspension and tinidazole tablets each given as a single 2 g bolus dose in an open controlled prospective study were found to be effective forms of treatment for Trichomonas vaginalis vaginitis. The cure rates on wet smear preparations were 100%, 100% and 94,8% respectively, and symptomatic and observed improvements were excellent. There was a statistically significant difference between the response rates associated with both metronidazole preparations and tinidazole. The results of this study indicate that single-dosage bolus therapy can confidently be recommended in trichomonal infections and that it has a number of advantages.
Shailendra Singh Solanki
Full Text Available Aceclofenac has been shown to have potent analgesic and anti-inflammatory activities similar to indomethacin and diclofenac, and due to its preferential Cox-2 blockade, it has a better safety than conventional Non steroidal anti-inflammatory drug (NSAIDs with respect to adverse effect on gastrointestinal and cardiovascular systems. Aceclofenac is superior from other NSAIDs as it has selectivity for Cox-2, a beneficial Cox inhibitor is well tolerated, has better Gastrointestinal (GI tolerability and improved cardiovascular safety when compared with other selective Cox-2 inhibitor. To provide the patient with the most convenient mode of administration, there is need to develop a fast-disintegrating dosage form, particularly one that disintegrates and dissolves/disperses in saliva and can be administered without water, anywhere, any time. Such tablets are also called as "melt in mouth tablet." Direct compression, freeze drying, sublimation, spray drying, tablet molding, disintegrant addition, and use of sugar-based excipients are technologies available for mouth-dissolving tablet. Mouth-dissolving tablets of aceclofenac were prepared with two different techniques, wet granulation and direct compression, in which different formulations were prepared with varying concentration of excipients. These tablets were evaluated for their friability, hardness, wetting time, and disintegration time; the drug release profile was studied in buffer Phosphate buffered Saline (PBS pH 7.4. Direct compression batch C3 gave far better dissolution than the wet granulation Batch F2, which released only 75.37% drug, and C3, which released 89.69% drug in 90 minutes.
Nakarani, Naresh V; Bhatt, Kashyap K; Patel, Rutva D; Bhatt, Hemaxi S
Two simple and accurate methods to determine atorvastatin calcium (ATO) and fenofibrate (FEN) in combined dosage forms were developed using second-derivative spectrophotometry and reversed-phase liquid chromatography (LC). ATO and FEN in combined preparations (tablets) were quantitated using the second-derivative responses at 245.64 nm for ATO and 289.56 nm for FEN in spectra of their solution in methanol. The calibration curves were linear [correlation coefficient (r) = 0.9992 for ATO and 0.9995 for FEN] in the concentration range of 3-15 microg/mL for ATO and FEN. In the LC method, analysis was performed on a Hypersil ODS-C18 column (250 mm x 4.6 mm id, 5 microm particle size) in the isocratic mode using the mobile phase methanol-water (90 + 10, v/v), adjusted to pH 5.5 with orthophosphoric acid, at a flow rate of 1 mL/min. Measurement was made at a wavelength of 246.72 nm. Both drugs were well resolved on the stationary phase, and the retention times were 1.95 min for ATO and 5.50 min for FEN. The calibration curves were linear (r = 0.9985 for ATO and 0.9976 for FEN) in the concentration range of 3-15 microg/mL for ATO and FEN. Both methods were validated, and the results were compared statistically. They were found to be accurate, precise, and specific. The methods were successfully applied to the estimation of ATO and FEN in combined tablet formulations.
Shankar, Madhira B; Modi, Vaibhav D; Shah, Dimal A; Bhatt, Kashyap K; Mehta, Rajendra S; Geetha, Madhira; Patel, Binita J
Two simple and accurate methods of analysis to determine pioglitazone hydrochloride (PIO) and mefformin hydrochloride (MET) in combined dosage forms were developed using second-derivative spectrophotometry and reversed-phase liquid chromatography (LC). PIO and MET in combined preparations (tablets) were quantified using the second-derivative responses at 227.55 nm for PIO and 257.25 nm for MET in spectra of their solutions in a mixture of methanol and acetonitrile (30 + 70). The calibration curves were linear [correlation coefficient (r) = 0.9984 for PIO and 0.9986 for MET] in the concentration range of 8-40 microg/mL for PIO and 4-12 microg/mL for MET. In the LC method, analysis was performed on a Hypersil ODS-C18 column with 5 microm particle size using the mobile phase acetonitrile-water-acetic acid (75 + 25 + 0.3), adjusted to pH 5.5 with liquor ammonia, at a flow rate of 0.5 mL/min. Measurement was made at a wavelength of 230 nm. Both the drugs were well resolved on the stationary phase, and the retention times were 8.5 min for PIO and 16.0 min for MET. The calibration curves were linear (r = 0.9933 for PIO and 0.9958 for MET) in the concentration range of 4-20 microg/mL for PIO and MET. Both methods were validated, and the results were compared statistically. They were found to be accurate, precise, and specific. The methods were successfully applied to the estimation of PIO and MET in combined tablet formulations.
L. I. Kucherenko
for nature of studied filming agents. Homogeneity in bulk of coated “Indotril” tablets also did not differ significantly as for filming agents’ nature. Divergence in mass of coated tablets did not differ significantly from uncoated ones; it testifies identity of filming process over all tablets surface. Strength of coated “Indotril” tablets as compared with uncoated ones increases in average on 15-20 H. Variance analysis of experimental data concerning tablets disintegration resistance showed that there was no significant difference between studied filming agents. While defining disintegration time statistical significance of filming agents’ nature was determined. Ranking is the following: 6% solution of HPMC Pharmacoat 603 > 5% solution of Opadray II WHITE > 5% solution of HPMC Pharmacoat 606 > 4% solution of HPMC Pharmacoat 615. But the difference between filming agents’ nature is not more than 2 minutes. Opadray II WHITE has been chosen for further study; it comes to the enterprise (“Arterium” Corporation where the results of investigation are planned to be introduced for the manufacture of other tablet dosage forms. On the next stage of our investigation we defined optimal values of quantitative factors, notably the influence of air temperature under gas distribution grid, concentration of film forming suspension and film thickness on the properties of coated “Indotril” tablets. Conclusion. Influence of filming agent nature on properties of coated tablets «Indotril» was studied, namely on appearance, homogeneity in bulk, mechanical strength, disintegration time. Opadray II WHITE was proposed for coating “Indotril” tablets by protective polymeric coat in pseudo-fluidized layer. Worked out formulation of filming agent solution and technology of its application were included into technological regulation of «Indotril» tablets production.
Alam, Md Tausif; Parvez, Nayyar; Sharma, Pramod Kumar
Oral route is the most preferred route for administration of different drugs because it is regarded as safest, most convenient, and economical route. Fast disintegrating tablets are very popular nowadays as they get dissolved or facilely disintegrated in mouth within few seconds of administration without the need of water. The disadvantages of conventional dosage form, especially dysphagia (arduousness in swallowing), in pediatric and geriatric patients have been overcome by fast dissolving tablets. Natural materials have advantages over synthetic ones since they are chemically inert, non-toxic, less expensive, biodegradable and widely available. Natural polymers like locust bean gum, banana powder, mango peel pectin, Mangifera indica gum, and Hibiscus rosa-sinenses mucilage ameliorate the properties of tablet and utilized as binder, diluent, and superdisintegrants increase the solubility of poorly water soluble drug, decrease the disintegration time, and provide nutritional supplement. Natural polymers are obtained from the natural origin and they are cost efficacious, nontoxic, biodegradable, eco-friendly, devoid of any side effect, renewable, and provide nutritional supplement. It is proved from the studies that natural polymers are more safe and efficacious than the synthetic polymers. The aim of the present article is to study the FDA-approved natural polymers utilized in fast dissolving tablets.
Clark, Elizabeth A; Alexander, Morgan R; Irvine, Derek J; Roberts, Clive J; Wallace, Martin J; Sharpe, Sonja; Yoo, Jae; Hague, Richard J M; Tuck, Chris J; Wildman, Ricky D
Additive manufacturing (AM) offers significant potential benefits in the field of drug delivery and pharmaceutical/medical device manufacture. Of AM processes, 3D inkjet printing enables precise deposition of a formulation, whilst offering the potential for significant scale up or scale out as a manufacturing platform. This work hypothesizes that suitable solvent based ink formulations can be developed that allow the production of solid dosage forms that meet the standards required for pharmaceutical tablets, whilst offering a platform for flexible and personalized manufacture. We demonstrate this using piezo-activated inkjetting to 3D print ropinirole hydrochloride. The tablets produced consist of a cross-linked poly(ethylene glycol diacrylate) (PEGDA) hydrogel matrix containing the drug, photoinitiated in a low oxygen environment using an aqueous solution of Irgacure 2959. At a Ropinirole HCl loading of 0.41mg, drug release from the tablet is shown to be Fickian. Raman and IR spectroscopy indicate a high degree of cross-linking and formation of an amorphous solid dispersion. This is the first publication of a UV inkjet 3D printed tablet. Consequently, this work opens the possibility for the translation of scalable, high precision and bespoke ink-jet based additive manufacturing to the pharmaceutical sector. Copyright © 2017. Published by Elsevier B.V.
Full Text Available The lactobacilli which are present in vaginal fluids play an important role in prevention of vaginosis and there are considerable interests in formulation of these friendly bacteria into suitable pharmaceutical dosage forms. Formulating these microorganisms for vaginal application is a critical issue as the products should retain viability of lactobacilli during formulation and also storage. The aim of this study was to examine the viability and release of Lactobacillus acidophilus from slow-release vaginal tablets prepared by using six different retarding polymers and from two effervescent tablets prepared by using citric or adipic acid. The Carbomer–based formulations showed high initial viablility compared to those based on HPMC-LV, HPMC-HV, Polycarbophil and SCMC polymers which showed one log decrease in viable cells. All retarding polymers in slow release formulations presented a strong bacterial release at about 2 h except Carbomer polymers which showed to be poor bacterial releasers. Although effervescent formulations produced a quick bacterial release in comparison with polymer based slow-release tablets, they were less stable in cold storage. Due to the strong chelating characteristic of citric acid, the viability was quickly lost for aqueous medium of citric acid in comparison with adipic acid based effervescent tablets.
Full Text Available Mark A WainbergMcGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, CanadaAbstract: A recent addition to the anti-human immunodeficiency virus armamentarium of drugs is rilpivirine, which is a potent non-nucleoside reverse transcriptase inhibitor. This review focuses on the clinical utility of rilpivirine in terms of efficacy and virologic suppression, drug resistance, drug-drug interactions, and safety. The rilpivirine-tenofovir-emtricitabine combination is a safe and effective regimen for use in most patients who are ready to start first-line anti-human immunodeficiency virus therapy. Although drug resistance can be a problem in patients who initiate therapy on rilpivirine-based regimens with viral loads > 100,000 copies of viral RNA/mL, this problem can be alleviated by first starting therapy with efavirenz-tenofovir-emtricitabine for several months to suppress viral load to <50 copies/mL before switching to rilpivirine-based therapy. E138K is the most important mutation associated with resistance against rilpivirine and its development must be avoided whenever possible, because this mutation confers broad cross-resistance against all approved members of the non-nucleoside reverse transcriptase inhibitor family of drugs.Keywords: non-nucleoside reverse transcriptase inhibitors, rilpivirine, human immunodeficiency virus, treatment, resistance
Vaughan, Alan; Collins, Nathan; Krus, Mike
Digital field mapping offers significant benefits when compared with traditional paper mapping techniques in that it provides closer integration with downstream geological modelling and analysis. It also provides the mapper with the ability to rapidly integrate new data with existing databases without the potential degradation caused by repeated manual transcription of numeric, graphical and meta-data. In order to achieve these benefits, a number of PC-based digital mapping tools are available which have been developed for specific communities, eg the BGS•SIGMA project, Midland Valley's FieldMove®, and a range of solutions based on ArcGIS® software, which can be combined with either traditional or digital orientation and data collection tools. However, with the now widespread availability of inexpensive tablets and smart phones, a user led demand for a fully integrated tablet mapping tool has arisen. This poster describes the development of a tablet-based mapping environment specifically designed for geologists. The challenge was to deliver a system that would feel sufficiently close to the flexibility of paper-based geological mapping while being implemented on a consumer communication and entertainment device. The first release of a tablet-based geological mapping system from this project is illustrated and will be shown as implemented on an iPad during the poster session. Midland Valley is pioneering tablet-based mapping and, along with its industrial and academic partners, will be using the application in field based projects throughout this year and will be integrating feedback in further developments of this technology.
Sudarshan B. Aher; Dattatraya M. Shinkar; Ravindra B. Saudagar
In the drug development enhancement of oral bioavailability of poorly water soluble drugs is one of the most challenging aspects of drug. The pharmaceutical industry face the problem poor dissolution characteristics of water insoluble drug. these problem solve by applying recent techniques “powdered solution technology” or “liquisolid technology”, for prepare water-insoluble drugs into rapid-release solid dosage forms. Design and formulation of this approach is prescribed according to new mat...
Shah, Dimal A; Bhatt, Kashyap K; Mehta, Rajendra S; Baldania, Sunil L
Two simple and accurate methods for analysis of nebivolol hydrochloride (NEB) and hydrochlorothiazide (HCTZ) in their combined dosage forms were developed using first-order derivative spectrophotometry and reversed-phase liquid chromatography (LC). NEB and HCTZ in their combined dosage forms (tablets) were quantified using first-derivative responses at 294.6 and 334.6 nm in the spectra of their solutions in methanol. The calibration curves were linear in the concentration range of 8-40 microg/mL for NEB and 10-60 microg/mL for HCTZ. LC analysis was performed on a Phenomenex Gemini C18 column (250 x 4.6 mm id, 5 microm particle size) in the isocratic mode with 0.05 M potassium dihydrogen phosphate-acetonitrile-methanol (30 + 20 + 50, v/v/v; pH 4) mobile phase at a flow rate of 1 mL/min. Detection was made at 220 nm. Both of the drugs and the internal standard (ezetimibe) were well resolved with retention times of 5.1 min for NEB, 2.9 min for HCTZ, and 8.2 min for ezetimibe. The calibration curves were linear in the concentration range of 1-14 microg/mL for NEB and 0.3-28 microg/mL for HCTZ. Both methods were validated and found to be accurate, precise, and specific, and results were compared statistically. Developed methods were successfully applied for the estimation of NEB and HCTZ in their combined dosage forms.
Full Text Available The objective of this study was to develop diazepam orally disintegrating tablets and to optimize tablets characteristics using response surface methodology (RSM. Tablets were prepared by direct compression of mixture containing mannitol, copovidone, crosspovidone flavor and lubricant. A full factorial design for 2 factors at 3 levels each was applied to investigate the influence of 2 formulation variables on the mechanical strength/hardness, the percent of friability, disintegration time and dissolution of the poorly soluble active ingredient. The amounts of copovidone and crosspovidone were taken as independent variables. All data were analyzed by using statistical program. The results of multiple linear regression analysis revealed that for obtaining a rapidly disintegrating dosage form, tablets should be prepared using an optimum concentration of crospovidone and copovidone. A contour plot is also presented to graphically represent the effect of the independent variables on the tablet hardness, disintegration time, percentage friability and dissolution. A checkpoint batch was also prepared to prove the validity of the evolved mathematical model. 3 level factorial design allowed us to obtain ODT with rapid disintegration and dissolution of the active ingredient with desirable properties of low tablet friability and appropriate mechanical strength (hardness of the tablet.
Oh, Mi Jin; Hwang, Hyun Hwan; Kim, Hyun Gyu; Lee, Geun Hyeog; Cho, Yun-Seok; Lee, Sun Young; Kang, Soo Yeon; Cho, Kyung Hee; Lee, Yun Young; Lee, Yun Jeong; Jang, Choon-Gon; Lee, Seok-Yong
A fixed-dose combination (FDC) pill of amlodipine (relatively old calcium channel blocker as dihydropyridine) and olmesartan (relatively new angiotensin II receptor blocker) is used for hypertension that is not adequately controlled with a single-formulation drug. Because the FDC is a one-pill formulation, and amlodipine and olmesartan have different mechanisms of action, it is expected to improve patients' medication compliance and have an increased blood pressure-lowering efficacy. The purpose of this study was to assess the safety profile and the bioequivalence of two different FDC formulations [amlodipine besylate/olmesartan medoxomil 10/40 mg (reference product) and S-amlodipine nicotinate/olmesartan medoxomil 5/40 mg (test product)]. A randomized, open-label, single-dose, 2-treatment, 2-way, and 2-period crossover study, including a 3-week washout period, was performed in 32 healthy Korean male volunteers. To analyze the concentration of S-amlodipine or olmesartan, plasma samples were collected up to 144 hours after the dose for S-amlodipine and 48 hours after the dose for olmesartan. Pharmacokinetic parameters, including the Cmax and the area under the curve from time 0 to the last measurable concentration (AUC0-last) for the time versus concentration plot, were calculated. Analysis of variance for bioequivalence was conducted using Cmax and AUC0-last converted to log scale, and the mean ratios and 90% CIs were determined. Safety data included analysis of adverse events (AEs), vital signs, physical examinations, clinical laboratory test, and 12-lead ECGs. Of the 32 enrolled participants, 29 healthy volunteers completed the study. For both S-amlodipine and olmesartan, the main pharmacokinetic parameters were all within the acceptable range for regulatory bioequivalence. The 90% CIs for the geometric mean ratios of Cmax and AUC0-last were 0.8766 to 0.9760 and 0.8288 to 0.9224, respectively, for S-amlodipine and 0.9097 to 1.1229 and 0.8904 to 1
Chen, Ying-Chen; Ho, Hsiu-O; Chiu, Chiao-Chi; Sheu, Ming-Thau
In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF) tablets to enhance its oral bioavailability. GRDF tablets were characterized with the effects of different molecular weights (MWs) of chitosan (CS) and hydroxyethyl cellulose (HEC) at various ratios on swelling, floating, and physical integrity. The CS component was formed using various acids: acetic, lactic, malic, succinic, and citric, and a high viscosity grade of HEC was selected. The results demonstrated that the swelling ratios of the formulations comprising high MW CS were lower than those of low or medium MW CS when salts were formed with any countering acids except for acetic acid. The decreasing ranking of the swelling rates was: CS-citrate > CS-malate > CS-lactate > CS-succinate > CS-acetate. A negative correlation was found between the pKa of the respective countering acid and the swelling rate. The swelling rate was promoted if an acidic salt of CS with a lower water content was incorporated, while it became slower when tablet hardness was higher or the compression force to form tablets was increased. Although HEC did not contribute to swelling or floating, it played a role in maintaining structural integrity. A prolonged dissolution profile of alendronate GRDF tablets developed in this study was observed.
Wang, Jie; Goyanes, Alvaro; Gaisford, Simon; Basit, Abdul W
The aim of this work was to evaluate the suitability of stereolithography (SLA) to fabricate drug-loaded tablets with modified-release characteristics. The SLA printer creates solid objects by using a laser beam to photopolymerise monomers. In this work polyethylene glycol diacrylate (PEGDA) was used as a monomer and diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide was used as a photo-initiator. 4-aminosalicylic acid (4-ASA) and paracetamol (acetaminophen) were selected as model drugs. Tablets were successfully printed and formulations with different properties were fabricated by adding polyethylene glycol 300 (PEG 300) to the printing solution. The loading of paracetamol and 4-ASA in the printed tablets was 5.69% and 5.40% respectively. In a realistic dynamic dissolution simulation of the gastrointestinal tract, drug release from the tablets was dependent on the composition of the formulations, but independent of dissolution pH. In conclusion SLA 3DP technology allows the manufacture of drug loaded tablets with specific extended-release profiles. In the future this technology could become a manufacturing technology for the elaboration of oral dosage forms, for industrial production or even for personalised dose. Copyright © 2016 Elsevier B.V. All rights reserved.
P. Venkata Reddy
Full Text Available A reverse phase HPLC method is developed for the determination of Raloxifene in pharmaceutical dosage forms. Chromatography was carried out on an inertsil C18 column using a mixture of acetonitrile and phosphate buffer (30:70 v/v as the mobile phase at a flow rate of 1 mL/min. Detection was carried out at 290 nm .The retention time of the drug was 10.609 min. The method produced linear responses in the concentration range of 0.5-200 µg/mL of Raloxifene. The method was found to be applicable for determination of the drug in tablets.
Yin, Xian-Zhen; Wu, Li; Li, Ying; Guo, Tao; Li, Hai-Yan; Xiao, Ti-Qiao; York, Peter; Nangia, Ashwini; Gui, Shuang-Ying; Zhang, Ji-Wen
The deformation behavior of particles under pressure dominates the mechanical properties of solid dosage forms. In this study, the in situ 3D deformation of two polymorphs (I and II) of clopidogrel bisulfate (CLP) was determined to illustrate pressure distribution profiles within the tablet by the deformation of the crystalline particles for the first time. Synchrotron radiation X-ray computed microtomography (SR-μCT) was utilized to visualize and quantify the morphology of thousands crystalline particles of CLP I and CLP II before and after compression. As a result, the deformation was examined across scale dimensions from microns to the size of the final dosage form. Three dimensional parameters such as volume, sphericity, oblate and prolate of individual particle and distributions were computed and analyzed for quantitative comparison to CLP I and CLP II. The different degrees of deformation under the same compression conditions of CLP I and CLP II were observed and characterized quantitatively. The map of deformation degrees within the tablet illustrated the heterogeneous pressure distribution in various regions of the compacted tablet. In conclusion, the polymorph deformation behaviors demonstrated by SR-μCT quantitative structure analysis deepen understanding of tableting across dimensions from microns to millimeters for the macrostrcuture of tablet.
Full Text Available One titrimetric and two spectrophotometric methods which are simple, selective, sensitive, accurate, precise and economical for the determination of etamsylate (ETM in bulk drug and in tablets employing permanganate as the oxidimetric reagent are described. In titrimetry, ETM is titrated directly with permanganate in sulphuric acid medium. A direct spectrophotometry (method A involves treating the aqueous solution of the drug with permanganate in alkaline medium and measuring the bluish green product at 610 nm. In indirect spectrophotometry (method B, the drug solution was treated with a fixed concentration of permanganate in H2SO4 medium, and after a specified time, the unreacted permanganate was measured at 545 nm. The molar combining ratio in titrimetry and the optimum assay conditions were studied. Titrimetry is applicable over 1–10 mg range and the calculations are based on a 1:4 (ETM:KMnO4 molar ratio. In spectrophotometry, Beer’s law is obeyed over 0.5- 5.0 and 1.5–15 μg ml-1 for method A and B, respectively. The molar absorptivity values are calculated to be 2.79104 and 4.17104 l mol-1 cm-1 for method A and B, respectively and the corresponding sandell sensitivity values are 0.0094 and 0.0063 μg cm-2. The limits of detection (LOD and quantification (LOQ are also reported for spectrophotometric methods. The applicability of the developed methods was demonstrated by the determination of etamsylate in pure drug as well as in commercial dosage forms.
Full Text Available This paper describes validated reverse phase high-performance liquid chromatographic (RP-HPLC method for simultaneous estimation of trihexyphenidyl hydrochloride (THP and risperidone (RSP in the pure powder form and in combined tablet dosage form. The HPLC separation was achieved on a core shell C18 (100 mm length × 4.6 mm, 2.6 μm particle size using methanol : ammonium acetate buffer 1% (85 : 15 v/v; pH-6.5 as mobile phase and delivered at flow rate of 0.8 mL/min. The calibration plot showed good linear relationship with r2 = 0.997 ± 0.001 for THP and r2 = 0.998 ± 0.001 for RSP in concentration range of 50–175 μg/mL and 50–175 μg/mL, respectively. LOD and LOQ were found to be 0.40 and 1.29 μg/mL for THP and 1.24 and 3.92 μg/mL for RSP. Assay of THP and RSP was found to be 100.16 ± 0.03% and 99.83 ± 0.02%, respectively. THP and RSP were subjected to different stress conditions (acidic, basic, oxidative, thermal, and photolytic degradation. The degraded product peaks were well resolved from the pure drug peak. The method was successfully validated as per the ICH guidelines. The developed RP-HPLC method was successfully applied for the estimation of THP and RSP in tablet dosage form.
Lorentzen, Rasmus Fink
Denne rapport afslutter CELMS undersøgelse af Odder Kommunes projekt med indførelse af iPads på alle kommunens skoler. Undersøgelsen har til formål at belyse om der er pædagogiske og læringsmæssige fordele forbundet med brugen af tablets i undervisningen i grundskolen og i givet fald hvilke...... designer og tablet’ens egenskaber i et generelt perspektiv. Rapporten afsluttes med en række anbefalinger til henholdsvis lærere og skoleledere med henblik på videre udvikling af indsatsen....
Fernanda Santos de Souza
Full Text Available Globules, compressed tablets and tablet triturates are solid dosage forms used in homeopathy. Divergences can be noted between the preparation techniques described in official compendiums as well as those applied in homeopathic pharmacies. The difficulty associated with standardization of the impregnation of these dosage forms occurs due to the lack of detail provided for the techniques in the literature, leaving it up to each pharmacy to decide on the exact method of preparation. The objective was to optimize the impregnation technique, through investigating the variables that influence the impregnation of globules, compressed tablets and tablet triturates, applying the statistical tool of factorial design. The independent variables were the dosage form, percentage and type of impregnation and drying temperature, and the dependent variables were the mass gain, disintegration time, friability and hardness. For the globules, the greatest mass gain was for 10% impregnation and drying at 20 ºC. For the tablet triturates and compressed tablets the greatest mass gain was for 15% impregnation and there was no difference between the results obtained using simple and triple impregnation or different drying temperatures. The results can contribute to improving the final product quality, besides aiding in the establishment of standardized techniques for the official compendiums.Glóbulos, comprimidos e tabletes são formas farmacêuticas sólidas utilizadas em homeopatia. Constatam-se divergências entre técnicas de preparação descritas nos compêndios oficiais, bem como em farmácias homeopáticas. A dificuldade de padronização na impregnação destas formas farmacêuticas também ocorre devido à falta de detalhamento das técnicas na literatura existente, deixando para cada farmácia a escolha de como executá-las. O objetivo foi otimizar a técnica de impregnação, através do estudo de variáveis que interferem na impregnação de gl
Pabari, Ritesh M; Ramtoola, Zebunnissa
A two factor, three level (3(2)) face centred, central composite design (CCD) was applied to investigate the main and interaction effects of tablet diameter and compression force (CF) on hardness, disintegration time (DT) and porosity of mannitol based orodispersible tablets (ODTs). Tablet diameters of 10, 13 and 15 mm, and CF of 10, 15 and 20 kN were studied. Results of multiple linear regression analysis show that both the tablet diameter and CF influence tablet characteristics. A negative value of regression coefficient for tablet diameter showed an inverse relationship with hardness and DT. A positive value of regression coefficient for CF indicated an increase in hardness and DT with increasing CF as a result of the decrease in tablet porosity. Interestingly, at the larger tablet diameter of 15 mm, while hardness increased and porosity decreased with an increase in CF, the DT was resistant to change. The optimised combination was a tablet of 15 mm diameter compressed at 15 kN showing a rapid DT of 37.7s and high hardness of 71.4N. Using these parameters, ODTs containing ibuprofen showed no significant change in DT (ANOVA; p>0.05) irrespective of the hydrophobicity of the ibuprofen. Copyright © 2012 Elsevier B.V. All rights reserved.
Just for you--Windows 8 from the tablet user's perspective If you're an experienced Windows user, you don't need a guide to everything that Windows 8 can do, just to those tools and functions that work on your tablet. And so here it is. This new book zeros in on what you need to know to work best on your tablet with Windows 8. Topics include navigating the new Windows 8 interface and how it works on a touchscreen, how to safely connect to the Internet, how to work with apps or share your tablet in a group, and much more. If you're a new tablet user, you'll particularly appre
Cvijić, Sandra; Aleksić, Ivana; Ibrić, Svetlana; Parojčić, Jelena
Consumption of alcoholic beverages with sustained-release oral dosage forms may pose a risk to patients due to potential alcohol-induced dose dumping (ADD). Regulatory guidances recommend in vitro dissolution testing to identify the risk of ADD, but the question remains whether currently proposed test conditions can be considered biopredictive. The purpose of this study was to evaluate different dissolution setups to assess ADD, and the potential of combined in vitro-in silico approach to predict drug absorption after concomitant alcohol intake for hydrophilic and lipophilic sustained-release tablets containing ibuprofen or diclofenac sodium. According to the obtained results, the impact of ethanol was predominantly governed by the influence on matrix integrity, with the increase in drug solubility being less significant. Hydrophilic matrix tablets were less susceptible to ADD than lipophilic matrices, although the conclusion on formulation ethanol-vulnerability depended on the employed experimental conditions. In silico predictions indicated that the observed changes in drug dissolution would not result in plasma concentrations beyond therapeutic window, but sustained-release characteristics of the formulations might be lost. Overall, the study demonstrated that in vitro-in silico approach may provide insight into the effect of ADD on drug clinical performance, and serve as a tool for ADD risk assessment.
Full Text Available Ying-Chen Chen,1,* Hsiu-O Ho,1,* Chiao-Chi Chiu,1 Ming-Thau Sheu1,2 1School of Pharmacy, College of Pharmacy, Taipei Medical University, 2Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan*These authors contributed equally to this workAbstract: In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF tablets to enhance its oral bioavailability. GRDF tablets were characterized with the effects of different molecular weights (MWs of chitosan (CS and hydroxyethyl cellulose (HEC at various ratios on swelling, floating, and physical integrity. The CS component was formed using various acids: acetic, lactic, malic, succinic, and citric, and a high viscosity grade of HEC was selected. The results demonstrated that the swelling ratios of the formulations comprising high MW CS were lower than those of low or medium MW CS when salts were formed with any countering acids except for acetic acid. The decreasing ranking of the swelling rates was: CS-citrate > CS-malate > CS-lactate > CS-succinate > CS-acetate. A negative correlation was found between the pKa of the respective countering acid and the swelling rate. The swelling rate was promoted if an acidic salt of CS with a lower water content was incorporated, while it became slower when tablet hardness was higher or the compression force to form tablets was increased. Although HEC did not contribute to swelling or floating, it played a role in maintaining structural integrity. A prolonged dissolution profile of alendronate GRDF tablets developed in this study was observed.Keywords: gastroretentive dosage form, chitosan, hydrogel, hydroxyethyl cellulose, swelling, alendronate
Effects of telmisartan combined with nifedipine controlled release tablet on inflammatory factors, vascular endothelial function and left ventricular function in patients with coronary heart disease with mild to moderate hypertension
Full Text Available Objective: To investigate the effect of telmisartan combined with Nifedipine Controlled Release Tablet on inflammatory factors, vascular endothelial function and left ventricular function in patients with coronary heart disease with mild to moderate hypertension. Methods: A total of 92 cases of patients with coronary heart disease with mild to moderate hypertension were selected as the object of observation, according to the random data table, they were divided into the control group (n=46 and observation group (n=46, and patients in the control group were treated with Nifedipine Controlled Release Table therapy, on this basis, the observation group patients were given telmisartan treatment, two groups were treated for 6 months. The levels of the blood pressure, inflammatory factors, vascular endothelial function and left ventricular function compared between the two groups before and after treatment. Results: There were no significant differences in the levels of SBP, DBP, hs-CRP, TNF-α, NO, ET-1, LVEF, LVEDD and LVESD in the two groups before treatment. After treatment, two groups of SBP, DBP, hs-CRP, TNF-α, ET-1, LVEDD and LVESD levels were significantly lower than those in the same group before treatment, and after treatment, the levels of SBP, DBP, hs-CRP, TNF-α, ET-1 and LVESD in the observation group were significantly lower than those in the control group, while there were no significant difference in the level of LVEDD between the two groups after treatment; Compared with level in the group before treatment, the levels of NO and LVEF in the two groups were significantly increased, and the observation group [(82.13±19.01 µmol/L, (52.83±7.45%] was significantly higher than the control group [(67.37±13.08 µmol/L, (49.47±6.96%]. Conclusion: Telmisartan combined with Nifedipine Controlled Release Table in treating coronary heart disease with mild to moderate hypertension, can effectively control blood pressure, reduce the
Hill, Laura L; Woodruff, Logan H; Foote, Jerald C; Barreto-Alcoba, Morela
Apple cider vinegar products are advertised in the popular press and over the Internet for treatment of a variety of conditions. After an adverse event was reported to the authors, eight apple cider vinegar tablet products were tested for pH, component acid content, and microbial growth. Considerable variability was found between the brands in tablet size, pH, component acid content, and label claims. Doubt remains as to whether apple cider vinegar was in fact an ingredient in the evaluated products. The inconsistency and inaccuracy in labeling, recommended dosages, and unsubstantiated health claims make it easy to question the quality of the products.
Sadia, Muzna; Sośnicka, Agata; Arafat, Basel; Isreb, Abdullah; Ahmed, Waqar; Kelarakis, Antonios; Alhnan, Mohamed A
This work aims to employ fused deposition modelling 3D printing to fabricate immediate release pharmaceutical tablets with several model drugs. It investigates the addition of non-melting filler to methacrylic matrix to facilitate FDM 3D printing and explore the impact of (i) the nature of filler, (ii) compatibility with the gears of the 3D printer and iii) polymer: filler ratio on the 3D printing process. Amongst the investigated fillers in this work, directly compressible lactose, spray-dried lactose and microcrystalline cellulose showed a level of degradation at 135°C whilst talc and TCP allowed consistent flow of the filament and a successful 3D printing of the tablet. A specially developed universal filament based on pharmaceutically approved methacrylic polymer (Eudragit EPO) and thermally stable filler, TCP (tribasic calcium phosphate) was optimised. Four model drugs with different physicochemical properties were included into ready-to-use mechanically stable tablets with immediate release properties. Following the two thermal processes (hot melt extrusion (HME) and fused deposition modelling (FDM) 3D printing), drug contents were 94.22%, 88.53%, 96.51% and 93.04% for 5-ASA, captopril, theophylline and prednisolone respectively. XRPD indicated that a fraction of 5-ASA, theophylline and prednisolone remained crystalline whilst captopril was in amorphous form. By combining the advantages of thermally stable pharmaceutically approved polymers and fillers, this unique approach provides a low cost production method for on demand manufacturing of individualised dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.
Full Text Available Pediatric, ibuprofen containing orodispersible tablets (ODTs were prepared using the SeDeM expert system methodology. In order to facilitate formulation, directly compressible ibuprofen was employed (Ibuprofen DC 8TM and characterized using its SeDeM profile. The mannitol based superdisintegrant Ludiflash® was characterized by the SeDeM-ODT expert system, which also allowed calculation of the optimal excipient concentration in order to obtain suitable tablet hardness and disintegration time. After adding a sweetener and a standard combination of lubricants, the optimized formulation was directly compressed into tablets and evaluated in terms of tablet hardness, friability, disintegration time and dissolution profile. The SeDeM method was applied to determine the amount of corrective excipient (Ludiflash® required for the compression of Ibuprofen DC 85TM in order to achieve suitable ODTs. Adequate tablet hardness, disintegration time, friability and dissolution profiles were found during tablet evaluation.
Alhnan, Mohamed A; Okwuosa, Tochukwu C; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel
The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.
Full Text Available Purpose: The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones. Methods: In this study, 13 formulations were prepared from potassium citrate and effervescent base in different concentration. The flowability of powders and granules was studied. Then effervescent tablets were prepared by direct compression, fusion and wet granulation methods. The prepared tablets were evaluated for hardness, friability, effervescent time, pH, content uniformity. To amend taste of formulations, different flavoring agents were used and then panel test was done by using Latin Square method by 30 volunteers. Results: Formulations obtained from direct compression and fusion methods had good flow but low hardness. Wet granulation improves flowability and other physicochemical properties such as acceptable hardness, effervescence time ≤3 minutes, pH<6, friability < 1%, water percentage < 0.5% and accurate content uniformity. In panel test, both of combination flavors; (orange - lemon and (strawberry - raspberry had good acceptability. Conclusion: The prepared tablets by wet granulation method using PVP solution had more tablet hardness. It is a reproducible process and suitable to produce granules that are compressed into effervescent tablets due to larger agglomerates.
Shah, Ritesh; Parmar, Swatil; Patel, Hetal; Pandey, Sonia; Shah, Dinesh
The purpose of present research work was to design and optimize compression coated tablet to provide an immediate release of hydrochlorothiazide in stomach and extended release of metoprolol succinate in intestine. Compression coated tablet was prepared by direct compression method which consisted of metoprolol succinate extended release core tablet and hydrochlorothiazide immediate release coat layer. Barrier coating of Hydroxy Propyl Methyl Cellulose (HPMC) E15LV was applied onto the core tablets to prevent burst release of metoprolol succinate in acidic medium. A 32 full factorial design was employed for optimization of the amount of polymers required to achieve extended release of drug. The percentage drug release at given time Q3, Q6, Q10, Q22; were selected as dependent variables. Core and compression coated tablets were evaluated for pharmaco-technical parameters. In vitro drug release of optimized batch was found to comply with Pharmacopoeial specifications. Desired release of metoprolol succinate was obtained by suitable combination of HPMC having high gelling capacity and polyethylene oxide having quick gelling capacity. The mechanism of release of metoprolol succinate from all batches was anomalous diffusion. Optimised batch was stable at accelerated conditions up to 3 months. Thus, compression coated tablet of metoprolol succinate and hydrochlorothiazide was successfully formulated.
al Gohary, O M; el Din, K; el Tahir, H
Double layer 325 mg oral aspirin tablets buffered with magaldrate antacid, 100, 150, 175 and 200 mg (F1, F2, F3 and F4, respectively) were prepared by direct compression. The new formulae were of remarkable hardness and friability. The tablets complied with the requirements of the acid neutralizing capacity, uniformity of dosage units, disintegration and dissolution tests (USP XXIII) for buffered aspirin tablets. The in vitro release pattern of F1 and F1 followed first order kinetics (r = 0.999), while F3 and F4 were released according to a zero order model (r = 0.993). Formulations F2, F3 and F4 as well as the marketed preparations, pure Aspro tablets (Acetylsalicylic acid 320 mg per tablet), or Ascriptin tablets (aspirin 325 mg plus 150 mg Maalox per tablet) were administered to fasted rats by gavage at doses that provided 400 mg aspirin kg-1 and the extent of the induced gastric damage was quantified 6 h later. Ascriptin, F3 and F4 preparations produced significantly less gastric damage (p < 0.05, n = 6) when compared with pure Aspro tablets. There was a clear dose-dependent decrease in the gastric damage following treatment with F2, F3 and F4 preparations, but there was no significant difference between the effects of F3 and F4 which were equipotent with Ascriptin.
Kindgen, Sarah; Rach, Regine; Nawroth, Thomas; Abrahamsson, Bertil; Langguth, Peter
A modified in vitro disintegration test device was designed that enables the investigation of the influence of hydrodynamic conditions on disintegration of solid oral dosage forms. The device represents an improved derivative of the compendial PhEur/USP disintegration test device. By the application of a computerized numerical control, a variety of physiologically relevant moving velocities and profiles can be applied. With the help of computational fluid dynamics, the hydrodynamic and mechanical forces present in the probe chamber were characterized for a variety of device moving speeds. Furthermore, a proof of concept study aimed at the investigation of the influence of hydrodynamic conditions on disintegration times of immediate release tablets. The experiments demonstrated the relevance of hydrodynamics for tablet disintegration, especially in media simulating the fasted state. Disintegration times increased with decreasing moving velocity. A correlation between experimentally determined disintegration times and computational fluid dynamics predicted shear stress on tablet surface was established. In conclusion, the modified disintegration test device is a valuable tool for biorelevant in vitro disintegration testing of solid oral dosage forms. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
Doreth, Maria; Hussein, Murtadha Abdul; Priemel, Petra A.
In situ amorphization is a concept that allows to amorphize a given drug in its final dosage form right before administration. Hence, this approach can potentially be used to circumvent recrystallization issues that other amorphous formulation approaches are facing during storage. In this study...... revealed that with increasing microwaving power and time, the fractions of crystalline IND and amorphous PVP reduced, whereas the amount of in situ formed IND-PVP glass solution increased. Intrinsic dissolution showed that the dissolution rate of the microwaved solid dispersion was similar...
Husic, Samir; Izic, Senad; Matic, Srecko; Sukalo, Aziz
The goal of the research was to determine the efficacy of a fixed combination of tramadol and paracetamol (acetaminophen) in the treatment of pain of patients with the advanced stage of cancer. A prospective study was conducted at the Center for Palliative Care, University Clinical Center Tuzla, Bosnia and Herzegovina, from January 1(st) to December 31(st) 2013. A total of 353 patients who were treated with a fixed combination of tramadol and acetaminophen (37.5 mg and 325 mg) at the initial dosage 3x1 tablet (112.5 mg tramadol and 975 mg acetaminophen) for pain intensity 4, up to 4x2 tablets (300 mg of tramadol and 2600 mg paracetamol) for pain intensity 7 and 8. If the patient during previous day has two or more pain episodes that required a "rescue dose" of tramadol, increased was the dose of fixed combination tramadol and acetaminophen to a maximum of 8 tablets daily (300 mg of tramadol and 2600 mg paracetamol). Statistical analysis was performed by biomedical software MedCalc for Windows version 188.8.131.52. The difference was considered significant for Pparacetamol). Side effects, in the treatment of pain with a fixed combination tramadol and acetaminophen, were found in 29.18% of patients, with a predominance of nausea and vomiting. Fixed combination of tramadol and acetaminophen can be used as an effective combination in the treatment of chronic cancer pain, with frequent dose evaluation and mild side effects.
Alanazi Amer M.
Full Text Available A simple, sensitive and accurate HPLC method with high throughput has been developed and validated for the simultaneous determination of irbesartan (IRB and hydrochlorothiazide (HCT in combined pharmaceutical dosage forms. The proposed method employed, for the first time, a monolithic column in the analysis. Optimal chromatographic separation of the analytes was achieved on Chromolith® Performance RP-18e column using a mobile phase consisting of phosphate buffer (pH 4/acetonitrile (50:50, V/V pumped isocratically at a flow rate of 1.0 mL min-1. The eluted analytes were monitored with a UV detector set at 270 nm. Under the optimum chromatographic conditions, linear relationship with a good correlation coefficient (R ≥ 0.9997 was found between the peak area and the corresponding concentrations of both IRB and HCT in the ranges of 10-200 and 1-20 ng mL-1. The limits of detection were 2.34 and 0.03 ng mL-1 for IRB and HCT, respectively. The intra- and inter-assay precisions were satisfactory as the RSD values did not exceed 3 %. The accuracy of the proposed method was > 97 %. The proposed method had high throughput as the analysis involved a simple procedure and a very short run- -time of < 3 min. The results demonstrated that the method is applicable in the quality control of combined pharmaceutical tablets containing IRB and HCT
Xu, Wenfeng; Wang, Haifeng; Chen, Gang; Li, Wen; Xiang, Rongwu; Zhang, Xiaoli; Pei, Yuehu
Niuhuang Jiedu Tablet (NJT), composed of Realgar (As₂S₂), Bovis Calculus Artificialis, Borneolum Synthcticum, Gypsum Fibrosum, Rhei Radix et Rhizoma (RR), Scutellariae Radix (SR), Platycodonis Radix (PR) and Glycyrrhizae Radix et Rhizoma (GR), is an effective formula of traditional Chinese medicine (TCM) used in treating acute tonsillitis, pharyngitis, periodontitis and mouth ulcer. In the formula, significant level of realgar (As₂S₂) as a potentially toxic element is contained. In our pervious experiments, NJT was significantly less toxic than realgar (As₂S₂), and the material bases of toxicity alleviation effect to realgar (As₂S₂) were RR, SR, PR and GR. However, the toxicity alleviation effect of each above mentioned four herbs to realgar (As₂S₂) and their synergistic detoxification effects to realgar (As₂S₂) were still obscure. Male Wistar rats were divided into 11 groups: control, group R (treated with Realgar), group RRSPG (treated with Realgar, RR, SR, PR and GR), group RRSP (treated with Realgar, RR, SR and PR), group RRSG (treated with Realgar, RR, SR and GR), group RRPG (treated with Realgar, RR, PR and GR), group RSPG (treated with Realgar, SR, PR and GR), group RR (treated with Realgar and RR), group RS (treated with Realgar and SR), group RP (treated with Realgar and PR) and group RG (treated with Realgar and GR). Based on (1)H NMR spectra of urine and serum from rats, PCA and PLS-DA were performed to identify different metabolic profiles. Liver and kidney histopathology examinations and serum clinical chemistry analysis were also performed. The metabolic profiles of groups RR, RS, RP and RG were similar to those of group R, while the metabolic profiles of groups RRSPG, RRSP, RRSG, RRPG and RSPG were almost in line with those of control group. Statistics results were confirmed by the histopathological examination and biochemical assay. The present work suggested that the toxicity alleviation effects of RR, SR, PR and GR to
Bhaskar, Aparajith; Barros, Fernando N; Singh, Ravendra
In the context of continuous pharmaceutical oral dosage manufacturing, a control system is essential to ensure that the critical quality attributes (CQAs) are maintained within the regulatory constraints by mitigating variations generated in upstream operations. Such a system is essential to the Quality by Design (QbD) paradigm shift, which can ensure that predefined end quality attributes are achieved within an optimal economic and time bracket. In this work, an advanced model predictive control (MPC) architecture integrated with a novel real-time tablet weight measurement method has been development and implemented into a continuous direct compaction tablet manufacturing pilot-plant. The proposed control architecture has the potential to control tablet weight and tablet breaking force simultaneously by systematically decoupling and cascading the control loops. The model predictive control algorithm was experimentally found to be superior to the PID (proportional, integral and derivative) controller and thus, can be utilized for a wide range of applications to improve the quality of pharmaceutical products in continuous manufacturing. The MPC was used to control main compression force and pre compression force using main compression height and fill depth respectively as the actuators. The introduction of this methodology leads to new ways of developing MPC models, tablet weight measurement methods and control strategies that enhance the manufacturability and quality of pharmaceutical tablets. Copyright © 2017 Elsevier B.V. All rights reserved.
Murad N. Abualhasan
Full Text Available Rutin is available in some foods, fruits, and vegetables. It has various beneficial medical effects making it useful in the treatment of various diseases. Rutin is available in different oral dosage forms such as tablets or capsules, widely available in the market. Rutin and many herbal medicines lack quality control due to unavailability of analytical methods. In this study, we formulated rutin tablet and studied its stability using a simple developed analytical method. The dissolution profile of our formulated tablet was also inspected. The results showed that our developed method was linear (R2=0.999, precise (% RSD = 0.026, and accurate (% recovery = 98.55–103.34. The formulated rutin tablet was stable under accelerated conditions as well as room temperature for 150 days (% assay > 91.69. The dissolution profile over 45 minutes of our formulated tablet showed a better dissolution (26.5% compared with the internationally marketed Rutin® tablet (18.5%. This study can serve as a guideline to companies that manufacture herbal products to improve their formulated herbs and apply validated analytical methods to check the quality of their product.
Full Text Available The present investigation studied a novel Bilayer tablet having extended release (ER system of metformin HCl (M.HCl with Eudragit RS 100 and RL 100 and immediate release (IR system of Acarbose with PVP K30 and PEG 6000 in different ratios using solvent evaporation technique. Solid dispersions (SDs were characterized by Fourier Transform-Infra Red spectroscopy, Diffrential Scanning Calorimetry, X-Ray Diffractometry and Scanning Electron Microscopy. Selected SD system was subjected to Bilayer tablet preparation by direct compression. Compressed tablets were evaluated for physical parameters, drug release and stability. SEM studies suggested the homogenous dispersion of the drug in polymers. FT-IR studies confirmed the formation of hydrogen bonding between the drug and polymer. XRD and DSC suggested the amorphous nature of the drug in SDs. All tablet formulations showed compliance with pharmacopoeial standards. In-vitro dissolution kinetics followed the Higuchi model via a non-fickian diffusion controlled release mechanism after the initial burst release. Stability studies conducted for optimized formulation did not show any change in the physical properties, drug content and drug release. Bilayer tablets showed an IR effect to provide the loading dose of the drug, followed by ER effect for 12 h, indicating a promising potential of the M.HCl and Acarbose Bilayer tablet as an alternative to the conventional dosage form.
Juban, Audrey; Briançon, Stéphanie; Puel, François; Hoc, Thierry; Nouguier-Lehon, Cécile
In the pharmaceutical field, tablets are the most common dosage form for oral administration in the world. Among different manufacturing processes, direct compression is widely used because of its economics interest and it is a process which avoids the steps of wet granulation and drying processes. Tablets are composed of at least two ingredients: an active pharmaceutical ingredient (API) which is mixed with a diluent. The nature of the powders and the processing conditions are crucial for the properties of the blend and, consequently, strongly influence the mechanical characteristics of tablets. Moreover, tablets have to present a suitable mechanical strength to avoid crumbling or breaking when handling, while ensuring an appropriate disintegration after administration. Accordingly, this mechanical property is an essential parameter to consider. Experimental results showed that proportion of the diluent, fragmentary (DCPA) or plastic (MCC), had a large influence on the tensile strength evolution with API content as well as the compression load applied during tableting process. From these results a model was developed in order to predict the tensile strength of binary tablets by knowing the compression pressure. The validity of this model was demonstrated for the two studied systems and a comparison was made with two existing models.
Full Text Available In the pharmaceutical field, tablets are the most common dosage form for oral administration in the world. Among different manufacturing processes, direct compression is widely used because of its economics interest and it is a process which avoids the steps of wet granulation and drying processes. Tablets are composed of at least two ingredients: an active pharmaceutical ingredient (API which is mixed with a diluent. The nature of the powders and the processing conditions are crucial for the properties of the blend and, consequently, strongly influence the mechanical characteristics of tablets. Moreover, tablets have to present a suitable mechanical strength to avoid crumbling or breaking when handling, while ensuring an appropriate disintegration after administration. Accordingly, this mechanical property is an essential parameter to consider. Experimental results showed that proportion of the diluent, fragmentary (DCPA or plastic (MCC, had a large influence on the tensile strength evolution with API content as well as the compression load applied during tableting process. From these results a model was developed in order to predict the tensile strength of binary tablets by knowing the compression pressure. The validity of this model was demonstrated for the two studied systems and a comparison was made with two existing models.
Young, Justin G; Trudeau, Matthieu B; Odell, Dan; Marinelli, Kim; Dennerlein, Jack T
Due to its rapid growth in popularity, there is an imminent need for ergonomic evaluation of the touch-screen tablet computing form-factor. The aim of this study was to assess postures of the shoulders and wrists and their associated muscle activity during touch-screen tablet use. Fifteen experienced adult tablet users completed a set of simulated software tasks on two media tablets in a total of seven user configurations. Configurations consisted of a combination of a support condition (held with one hand, two hands or in a case), a location (on the lap or table surface), and a software task (web browsing, email, and game). Shoulder postures were measured by using an infra-red LED marker based motion analysis system, wrist postures by electro-goniometry, and shoulder (upper trapezius and anterior deltoid) and forearm (flexor carpi radialis, flexor carp ulnaris, and extensor radialis) muscle activity by surface electromyography. Postures and muscle activity for the wrist significantly varied across configurations and between hands, but not across the two tablets tested. Wrist extension was high for all configurations and particularly for the dominant hand when a tablet was placed on the lap (mean=38°). Software tasks involving the virtual keyboard (e-mailing) corresponded to higher wrist extensor muscle activity (50th percentile=9.5% MVC) and wrist flexion/extension acceleration (mean=322°/s2). High levels of wrist radial deviation were observed for the non-dominant hand when it was used to tilt and hold the tablet (mean=13°). Observed differences in posture and muscle activity of the shoulder were driven by tablet location. Touch-screen tablet users are exposed to extreme wrist postures that are less neutral than other computing technologies and may be at greater risk of developing musculoskeletal symptoms. Tablets should be placed in cases or stands that adjust the tilt of the screen rather than supporting and tilting the tablet with only one hand.
In Hong Kong, 627 adult Chinese patients with newly diagnosed pulmonary tuberculosis received, for the first 2 months of chemotherapy, streptomycin together with isoniazid, rifampin, and pyrazinamide allocated at random to be given either as a combined formulation or separately. Each tablet of the combined formulation, which was designed for intermittent use, contained 125 mg of isoniazid, 100 mg of rifampin, and 375 mg of pyrazinamide. Patients weighing 42 kg or less received 5 tablets per dose, 43 to 57 kg, 6 tablets per dose, and 58 kg or more, 7 tablets per dose. The dosage of each drug was very similar whether it was given combined or separately. During the 2 months, spontaneous complaints, the commonest of which were nausea and vomiting, were made by 38% of patients receiving the combined and 39% receiving the separate formulations; 1% compared with 5%, respectively, complained that the tablets or capsules were too many, too large, difficult to swallow or that they stuck in the throat (p less than 0.05), and 32% compared with 45% regularly brought their own drink (usually milk or fruit juice) to the clinic to help them swallow their medicament (p less than 0.01). Only 14% of patients in each group missed one or more doses through default. Reported adverse reactions were mainly trivial, 4% of patients receiving the combined and 7% receiving the separate formulations having the administration of one or more drugs terminated. Thus, the differences between the combined and separate formulations showed a small advantage to the combined formulation in terms of acceptability to patients.
Pilachowski, Catherine A.; Morris, Frank
Open prospective study to evaluate cardiovascular risk factors and renal function in 2 dosage regimens of tacrolimus combined with mycophenolate mofetil and steroids in renal transplant patients: 5-year results.
Chamienia, A; Dębska-Ślizień, A; Król, E; Biedunkiewicz, B; Rutkowski, B
Cyclosporine and tacrolimus (TAC) are the most potent immunosuppressants. TAC is considered less nephrotoxic, but may be an important factor in chronic graft dysfunction. The aim of the study was to evaluate kidney function and cardiovascular risk profile in 2 groups of low immunological risk kidney allograft recipients receiving 2 TAC dosages. Patients were randomly assigned to 2 TAC-based treatments (group I [n = 14], standard dose; group II [n = 15], reduced dose). Patient and graft survival, graft function, occurrence of cardiovascular events (cardiac death, myocardial infarction, stroke), incidence of new-onset diabetes mellitus after transplantation, and cardiovascular risk factors were assessed over a 5-year period. Patient demographics and transplant characteristics were not statistically different between groups. TAC trough levels were significantly higher in group I for 24 months post transplant. Patient survival did not differ, but there were more acute rejection episodes and graft losses in group II. There were no significant differences in the rate of cardiac events. Graft function measured as serum creatinine levels and calculated glomerular filtration rate did not differ between groups. The same applies to new-onset diabetes mellitus after transplantation incidence. Office blood pressures were numerically higher in group I up to 24 months but this difference did not reach significance at any time. Similar results were obtained for serum lipids. Immunosuppression based on low doses of tacrolimus seems to be safe in the group of low immunological risk patients but in the 60-month follow-up does not offer any clear benefits in terms of potential nephrotoxicity or cardiovascular risk.
Klukkert, Marten; Wu, Jian X; Rantanen, Jukka; Carstensen, Jens M; Rades, Thomas; Leopold, Claudia S
Monitoring of tablet quality attributes in direct vicinity of the production process requires analytical techniques that allow fast, non-destructive, and accurate tablet characterization. The overall objective of this study was to investigate the applicability of multispectral UV imaging as a reliable, rapid technique for estimation of the tablet API content and tablet hardness, as well as determination of tablet intactness and the tablet surface density profile. One of the aims was to establish an image analysis approach based on multivariate image analysis and pattern recognition to evaluate the potential of UV imaging for automatized quality control of tablets with respect to their intactness and surface density profile. Various tablets of different composition and different quality regarding their API content, radial tensile strength, intactness, and surface density profile were prepared using an eccentric as well as a rotary tablet press at compression pressures from 20MPa up to 410MPa. It was found, that UV imaging can provide both, relevant information on chemical and physical tablet attributes. The tablet API content and radial tensile strength could be estimated by UV imaging combined with partial least squares analysis. Furthermore, an image analysis routine was developed and successfully applied to the UV images that provided qualitative information on physical tablet surface properties such as intactness and surface density profiles, as well as quantitative information on variations in the surface density. In conclusion, this study demonstrates that UV imaging combined with image analysis is an effective and non-destructive method to determine chemical and physical quality attributes of tablets and is a promising approach for (near) real-time monitoring of the tablet compaction process and formulation optimization purposes. Copyright © 2015 Elsevier B.V. All rights reserved.
Nekkanti, Vijaykumar; Pillai, Raviraj; Venkateshwarlu, Vobalaboina; Harisudhan, T
Sparingly water-soluble drugs such as candesartan cilexetil offer challenges in developing a drug product with adequate bioavailability. The objective of the present study was to develop a tablet dosage form of candesartan cilexetil incorporating drug nanoparticles to increase its saturation solubility and dissolution rate for enhancing bioavailability while reducing variability in systemic exposure. The bioavailability of candesartan cilexetil is dissolution limited following oral administration. To enhance bioavailability and overcome variability in systemic exposure, a nanoparticle formulation of candesartan cilexetil was developed. Candesartan cilexetil nanoparticles were prepared using a wet bead milling technique. The milled nanosuspension was converted into solid intermediate using a spray drying process. The nanosuspensions were characterized for particle size before and after spray drying. The spray dried nanoparticles were blended with excipients for tableting. The saturation solubility and dissolution characteristics of the nanoparticle formulation were investigated and compared with commercial candesartan cilexetil formulation. The drug nanoparticles were evaluated for solid-state transitions before and after milling. This study demonstrated that tablet formulation incorporating drug nanoparticles showed significantly faster rate of drug dissolution in a discriminating dissolution medium as compared to commercially available tablet formulation. Systemic exposure studies in rats indicated a significant increase in the rate and extent of drug absorption.
Sun, Fei; Xu, Bing; Zhang, Yi; Dai, Shengyun; Shi, Xinyuan; Qiao, Yanjiang
The dissolution is one of the critical quality attributes (CQAs) of oral solid dosage forms because it relates to the absorption of drug. In this paper, the influence of raw materials, granules and process parameters on the dissolution of paracetamol tablet was analyzed using latent variable modeling methods. The variability in raw materials and granules was understood based on the principle component analysis (PCA), respectively. A multi-block partial least squares (MBPLS) model was used to ...
Wei, X H; Wu, J J; Liang, W Q
To use the artificial neural network (ANN) in Matlab 5.1 tool-boxes to predict the formulations of sustained-release tablets. The solubilities of nine drugs and various ratios of HPMC: Dextrin for 63 tablet formulations were used as the ANN model input, and in vitro accumulation released at 6 sampling times were used as output. The ANN model was constructed by selecting the optimal number of iterations (25) and model structure in which there are one hidden layer and five hidden layer nodes. The optimized ANN model was used for prediction of formulation based on desired target in vitro dissolution-time profiles. ANN predicted profiles based on ANN predicted formulations were closely similar to the target profiles. The ANN could be used for predicting the dissolution profiles of sustained release dosage form and for the design of optimal formulation.
Full Text Available Background: Ritonavir is a protease inhibitor and mostly used as a booster for increasing the bioavailability of other protease inhibitors like Atazanavir Sulfate and Lopinavir. Aims: Quality assessment of the new dosage form of Ritonavir i.e. tablets is very essential, so two sensitive, simple and precise methods are developed for quantification of Ritonavir in bulk and tablet dosage forms. Materials and Methods: The first method is based on first order derivative method and the second is based on area under curve method. Both the methods are validated according to international conference of harmonization (ICH guidelines. A stability study of Ritonavir is done in UV - Visible Spectrophotometer under different stress conditions recommended by ICH guidelines. Results: The absorption maximum is found to be 239nm in methanol. The absorption maximum in first method is chosen at 253.2nm, and the linearity is found between 4 - 20 ΅g/ml with coefficient of correlation value 0.9981. In the second method, the range for area under curve selected is 237 - 242nm. The linearity is found between 4 -20 ΅g/ml with coefficient of correlation value 0.9992. Conclusion: The developed methods are validated and found to be simple, rapid, precise and cost-effective. The degradation study in tablet dosage form can be used as a stability indicating assay method.
Bendas, Ehab R; Christensen, J Mark; Ayres, James W
The basic objective of this study was to develop a novel technique that aids in compaction of coated pellets into tablets and obtain a release pattern from compressed pellets resembling the same pattern before compression. Multi-unit dosage forms of mesalamine targeted to the colon were formulated by extrusion-spheronization, and then coated with Eudragit S (30%). These pellets were filled into gelatin capsules or further formulated and compressed into tablets. Tablets for colonic delivery of mesalamine were prepared by mixing the coated beads with cushioning agents like stearic acid and Explotab, or by applying an additional coat of gelatin (4% weight gain) onto the Eudragit S coated pellets, and then compressing into tablets (tableted reservoir-type pellets). Then additional coating of the tablets prepared by the coating technique was applied utilizing Eudragit L 100-55 (5% weight gain). This technique provides additive protection for the coated beads to withstand the compression force during tableting. Excellent in vitro dissolution results were obtained, which were comparable to the results of the release of mesalamine from uncompressed beads filled in capsules. Mesalamine release from the capsules was 0.3% after 2 hours in gastric pH, 0.37% was released after an additional 1 hour in pH 6, and 89% was released after 1.5 hours in colonic pH 7.2. Various formulation and process parameters have to be optimized in order to obtain tableted reservoir-type pellets having the same release properties as the uncompressed pellets. The coating technique delays the release of mesalamine until the beads reach the terminal ileum and colon. Once released in the colon, mesalamine is minimally absorbed and can act locally to treat ulcerative colitis.
Winsemius, A; Meuwsen, I M; Boon, C; van der Laan, A; Brekle, A; de Vries, M
This study was conducted to compare the pharmacokinetic properties of the modified release 200 mg capsule of mebeverine and the plain 135 mg tablet of mebeverine after single and multiple doses in 12 healthy subjects in a randomised, crossover design. Single doses were given on days 1 and 7 and multiple doses (200 mg b.i.d. for the capsule and 135 mg t.i.d. for the tablet) on days 2-6 of the study. The 200 mg modified release capsule of mebeverine has extended release properties, as indicated by a lower Cmax, a later tmax and a longer elimination half-life than the plain tablet, while the bioavailability is optimal. No significant accumulation occurs after multiple doses of either formulation. The twice-daily dosage regimen of the 200 mg modified release capsule is a good alternative to the three times daily dosage regimen of the 135 mg plain tablet, because the reduced daily intake is likely to benefit patient compliance.
Dhiman, Neha; Awasthi, Rajendra; Jindal, Shammy; Khatri, Smriti; Dua, Kamal
The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose. The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin. The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation. All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h). Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.
Full Text Available The aim of this investigation was to develop fast dissolving tablet of cinnarizine. A combination of super disintegrants, i.e., sodium starch glycolate (SSG and crosscarmellose sodium (CCS were used along with camphor as a subliming material. An optimized concentration of camphor was added to aid the porosity of the tablet. A 3 2 full factorial design was applied to investigate the combined effect of two formulation variables: Amount of SSG and CCS. Infrared (IR spectroscopy was performed to identify the physicochemical interaction between drug and polymer. IR spectroscopy showed that there is no interaction of drug with polymer. In the present study, direct compression was used to prepare the tablets. The powder mixtures were compressed into tablet using flat face multi punch tablet machine. Camphor was sublimed from the tablet by exposing the tablet to vacuum drier at 60°C for 12 hours. All the formulations were evaluated for their characteristics such as average weight, hardness, wetting time, friability, content uniformity, dispersion time (DT, and dissolution rate. An optimized tablet formulation (F 9 was found to have good hardness of 3.30 ± 0.10 kg/cm 2 , wetting time of 42.33 ± 4.04 seconds, DT of 34.67 ± 1.53 seconds, and cumulative drug release of not less than 99% in 16 minutes.
Full Text Available A simple and sensitive extractive spectrophometric method has been described for the assay of oxaprozin (OXA either in pure form or in pharmaceutical solid dosage form. The developed method involves formation of colored chloroform extractable ion-pair complex of OXA with bromocresol green in aqueous acidic medium. The extracted complexes showed absorbance maxima at 421 nm. Beer's law is obeyed in the concentration range of 10-50 μg mL-1. This method has been applied to the determination of drug in commercial tablets. Results of analysis were validated statistically. The excipients present in the formulations do not interfere with the assay procedure.
Klukkert, Marten; Wu, Jian X; Rantanen, Jukka
with partial least squares analysis. Furthermore, an image analysis routine was developed and successfully applied to the UV images that provided qualitative information on physical tablet surface properties such as intactness and surface density profiles, as well as quantitative information on variations...... an eccentric as well as a rotary tablet press at compression pressures from 20MPa up to 410MPa. It was found, that UV imaging can provide both, relevant information on chemical and physical tablet attributes. The tablet API content and radial tensile strength could be estimated by UV imaging combined...... in the surface density. In conclusion, this study demonstrates that UV imaging combined with image analysis is an effective and non-destructive method to determine chemical and physical quality attributes of tablets and is a promising approach for (near) real-time monitoring of the tablet compaction process...
Bhusari, K. P.; Khedekar, P. B.; Dhole, Seema; Banode, V. S.
Two methods for simultaneous estimation of hydrochlorothiazide and olmesartan medoxomil in combined tablet dosage form have been developed. The first method is the application of Q–analysis method (absorbance ratio), which involves the formation of Q–absorbance equation at 264 nm (isobestic point) and at 271 nm, the maximum absorption of hydrochlorothiazide. The linearity ranges for hydrochlorothiazide and olmesartan medoxomil were 2.5-22.5 μg/ml and 4-36 μg/ml, respectively. The second method is based on the derivative spectrophotometric method at zero crossing wavelengths. The linearity ranges for hydrochlorothiazide and olmesartan medoxomil were 2.5-20 μg/ml and 4-32 μg/ml, respectively. The accuracy of the methods were assessed by recovery studies and was found to be 100.45% ±0.4215 and 100.24% ±0.3783 for absorbance ratio method and 99.39% ±0.221 and 99.72% ±0.11 for first derivative method, for hydrochlorothiazide and olmesartan medoxomil, respectively. These methods are simple, accurate and rapid, those require no preliminary separation and can therefore be used for routine analysis of both drugs in quality control laboratories. PMID:20502567
Singh, S; Jain, S; Muthu, M S; Tilak, R
Buccal bioadhesive tablets of clotrimazole (CTZ) and clotrimazole: hydroxypropyl-beta-cyclodextrin (CTZ-HPbetaCD) complex were prepared by using polymer xanthan gum in combination with carbopol 974P. The prepared buccal bioadhesive tablet formulations were evaluated for physicochemical characteristics (weight, hardness, friability, diameter, and drug content), swelling index, microenvironment pH, in-vitro drug release, bioadhesion strength, residence time and duration of antifungal activity (in-vitro). The dissolution of CTZ from the prepared tablets into phosphate buffer (pH 6.8) was controlled up to 8 h. All the prepared tablets gave reasonable in-vitro residence time (7.13 - 9.34 h). X-ray diffraction (XRD) studies of the CTZ-HPbetaCD complex, made by kneading and freeze-dried method, showed no CTZ crystal signals, demonstrating the inclusion of CTZ in the hydrophobic cavity of hydroxypropyl-beta-cyclodextrin (HPbetaCD) and formation of amorphous inclusion complex. Duration of the antifungal activity was measured by the inhibition zone of Candida albicans by agar diffusion assay. It is evident from the results obtained, the prepared buccal bioadhesive tablets of CTZ would markedly prolong the duration of the antifungal activity and may prove to be a viable alternative to the conventional local oral medication.
Allesø, Morten; Holm, Per; Carstensen, Jens Michael; Holm, René
Surface topography, in the context of surface smoothness/roughness, was investigated by the use of an image analysis technique, MultiRay™, related to photometric stereo, on different tablet batches manufactured either by direct compression or roller compaction. In the present study, oblique illumination of the tablet (darkfield) was considered and the area of cracks and pores in the surface was used as a measure of tablet surface topography; the higher a value, the rougher the surface. The investigations demonstrated a high precision of the proposed technique, which was able to rapidly (within milliseconds) and quantitatively measure the obtained surface topography of the produced tablets. Compaction history, in the form of applied roll force and tablet punch pressure, was also reflected in the measured smoothness of the tablet surfaces. Generally it was found that a higher degree of plastic deformation of the microcrystalline cellulose resulted in a smoother tablet surface. This altogether demonstrated that the technique provides the pharmaceutical developer with a reliable, quantitative response parameter for visual appearance of solid dosage forms, which may be used for process and ultimately product optimization. Copyright © 2015 Elsevier B.V. All rights reserved.
Gajendran, Jayachandar; Krämer, Johannes; Shah, Vinod P; Langguth, Peter; Polli, James; Mehta, Mehul; Groot, D W; Cristofoletti, Rodrigo; Abrahamsson, Bertil; Dressman, Jennifer B
Literature data relevant to the biopharmaceutical properties of the active pharmaceutical ingredient (API) nifedipine are reviewed to evaluate whether a waiver of in vivo bioequivalence (BE) testing of immediate-release (IR) dosage forms formulated as tablets and soft gelatin capsules is warranted. Nifedipine's solubility and permeability, its therapeutic use and index, pharmacokinetics, food drug interactions, and any reported BE/bioavailability problems were all taken into consideration. Solubility and BA data indicate conclusively that nifedipine is a class II substance of biopharmaceutics classification system (BCS) and that the formulation of drug product plays a key role on the dissolution characteristics of the API. Therefore, a BCS biowaiver-based approval of nifedipine containing IR oral dosage forms cannot be recommended for reformulated/new multisource drug products or for major scale-up and postapproval changes to the existing drug products. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.
Dorlo, Thomas P. C.; Kager, Piet A.
Pentamidine has a long history in the treatment of human African trypanosomiasis (HAT) and leishmaniasis. Early guidelines on the dosage of pentamidine were based on the base-moiety of the two different formulations available. Confusion on the dosage of pentamidine arose from a different labelling
... postulated the origin of the Y chromosome as having resulted from restricted recombination between homologous sex chromosomes in the male and the accumulation of deleterious mutations. This evolutionary process leads to dosage compensation. This article lays out a brief history of dosage compensation in genetics.
Allen, Loyd V
Drugs must be properly formulated for administration to patients, regardless of age. Pediatric patients provide some additional challenges to the formulator in terms of compliance and therapeutic efficacy. Due to the lack of sufficient drug products for the pediatric population, the pharmaceutical industry and compounding pharmacies must develop and provide appropriate medications designed for children. The purpose of this article was to review the physical, chemical, and biological characteristics of drug substances and pharmaceutical ingredients to be used in preparing a drug product. In addition, stability, appearance, palatability, flavoring, sweetening, coloring, preservation, packaging, and storage are discussed. Information for the current article was gathered from a literature review; from presentations at professional and technical meetings; and from lectures, books, and publications of the author, as well as from his professional experience. Professional society meetings and standards-setting bodies were also used as a resource. The proper design and formulation of a dosage form requires consideration of the physical, chemical, and biological characteristics of all of the drug substances and pharmaceutical ingredients (excipients) to be used in fabricating the product. The drug and pharmaceutical materials utilized must be compatible and produce a drug product that is stable, efficacious, palatable, easy to administer, and well tolerated. Preformulation factors include physical properties such as particle size, crystalline structure, melting point, solubility, partition coefficient, dissolution, membrane permeability, dissociation constants, and drug stability. Successful development of a formulation includes multiple considerations involving the drug, excipients, compliance, storage, packaging, and stability, as well as patient considerations of taste, appearance, and palatability.
Full Text Available Cilazapril, a moisture-sensitive compound, is known to undergo rapid degradation which could be additionally facilitated by the presence of excipients that contain or absorb moisture. Hence we investigated the stability of cilazapril in two commercially-available dosage forms and in binary mixtures with the selected excipients used in the studied commercial formulations i.e.: hypromellose, lactose monohydrate, maize starch and talc in order to detect any possible, stability-affecting incompatibilities. Also the impact of the blister made of oriented polyamide/aluminum/polyvinyl chloride//aluminum on cilazapril-containing tablets was researched. A validated HPLC and HPLC-MS methods were used for analysis and the isothermal stress testing conditions were applied (temperature range 318–343 K, relative humidity 76.4% for tablets and temperature 333 K, relative humidity range 50.9–76.4% for binary mixtures. It was shown that the degradation of cilazapril in both, model mixtures and tablets follows the autocatalytic model kinetics and it is more rapid than that observed for pure substance, evidenced by higher degradation rate constants. The immediate packaging protects cilazapril in tablets from degradation only in case of the original drug while in its blistered generic counterpart a slight but statistically insignificant increase of cilazapril decay occurs when compared to bare tablets (p < 0.05. The degradation product of cilazapril in tablets and binary mixtures was identified as cilazaprilat. It was also observed that the increase of relative humidity or the presence of hypromellose, lactose and talc significantly impairs the stability of cilazapril in the aforementioned order. Only maize starch exhibited a positive effect on cilazapril stability (10.8% loss of cilazapril in binary mixture after 360 days of stressing compared to 35% loss of pure cilazapril in analogous test conditions probably thanks to its moisture-scavenging properties
Many patients find it difficult to swallow tablets and hard gelatin capsules and do not take their medication as prescribed. It is estimated that 50% of the population is affected by this problem which results in a high incidence of non-compliance and ineffective therapy. The difficulty is experienced in particular by paediatric and geriatric patients, but it also applies to people who are ill in bed and to those active working patients who are busy or travelling, especially those who have no access to water. Such problems can be resolved by means of the Zydis dosage form which does not require water to aid swallowing. The Zydis fast-dissolving dosage form is a unique freeze dried medicinal tablet, made from well known and acceptable materials. When Zydis units are put into the mouth, the freeze dried structure disintegrates instantaneously releasing the drug which dissolves or disperses in the saliva. The saliva containing the dissolved or dispersed medicament is then swallowed and the drug is absorbed in the normal way. Some drugs are absorbed from the mouth, pharynx and oesophagus as the saliva passes down into the stomach. In these cases, the bioavailabilities of drugs from Zydis formulations are significantly greater than those observed from standard dosage forms. This paper deals with the formulation and process technology of the Zydis dosage form. The bioavailability characteristics of Zydis products are summarized, and in particular, the design of Zydis products for the enhancement of oral bioavailability and the improvement of clinical activity, through transmucosal delivery and pregastric absorption, is discussed.
Rao, Venkatramana M; Zannou, Erika A; Stella, Valentino J
The challenge of designing a delayed-release oral dosage form is significantly increased when the drug substance is poorly water soluble. This manuscript describes the design and characterization of a novel controlled-release film-coated tablet for the pH-triggered delayed and complete release of poorly water-soluble weak base drugs. Delivery of weak bases is specifically highlighted with the use of dipyridamole and prazosin as model compounds. Tailored delayed release is achieved with a combination of an insoluble but semipermeable polymer and an enteric polymer, such as cellulose acetate and hydroxypropyl cellulose phthalate, respectively, as coatings. The extent of the time lag prior to complete release depends on the film-coating composition and thickness. Complete release is achieved by the addition of a cyclodextrin, namely SBE7M-β-CD with or without a pH modifier added to the tablet core to ensure complete solubilization and release of the drug substance. The film-coating properties allow the complex formation/solubilization to occur in situ. Additionally, the drug release rate can be modulated on the basis of the cyclodextrin to drug molar ratio. This approach offers a platform technology for delayed release of potent but poorly soluble drugs and the release can be modulated by adjusting the film-coating composition and thickness and/or the cyclodextrin and pH modifier, if necessary. Copyright © 2010 Wiley-Liss, Inc.
Purpose: To formulate mucoadhesive chlorhexidine tablets and evaluate their drug release characteristics and mechanism. Methods: Chlorhexidine buccal adhesive tablets were prepared by direct compression using a blend of hydroxypropyl methylcellulose (HPMC) and chitosan as the bioadhesive polymers.
Purpose: To develop mucoadhesive tablets containing miconazole (MCZ) for the treatment of oropharyngeal candidiasis, using chitosan and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Methods: Mucoadhesive tablets were formulated and optimized using a 23 factorial design and direct ...
Purpose: To develop mucoadhesive tablets containing miconazole (MCZ) for the treatment of oropharyngeal candidiasis, using chitosan and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Methods: Mucoadhesive tablets were formulated and optimized using a 23 factorial design and direct.
Purpose: To formulate simvastatin orodispersible tablets with high dissolution rate and enhanced bioavailability. ... DSC and FTIR indicated the formation of solid dispersion without chemical interaction between simvastatin and polymer. Orodispersible tablet prepared with Emcosoy and Pullulan showed least wetting and.
Ali Akbar Ansarin; Farahman Farrokhi; Hamid Reza Mahboudi; Zohreh Adeli Jam
This paper examines the perceptions of advantages of smart phones and tablets on basic and general English students' language learning, self-sufficiency, and interest using smart phones and tablets...
Wang, Zhen; Du, Shou-ying; Lu, Yang; Zhao, Zhuang; Bai, Jie; Li, Peng-yue; Dong, Bo-yu; Du, Qin; Zhang, Lin
The borneol was included with β-CD and prepared Fufang Danshen intestinal adhesion pellets. GC method for determination of borneol in Fufang Danshen intestinal adhesion pellets was established to study its in vitro dissolution and make a comparison with the Fufang Danshen tablet, in this way, the rationality of dosage form was evaluated. The first method of dissolution determination was used for determining the in vitro dissolution of borneol in Fufang Danshen intestinal adhesion pellets in artificial intestinal juice, and Fufang Danshen tablet in artificial gastric juice and intestinal juice, respectively. Result shows: the concentration of borneol in Fufang Danshen intestinal adhesion pellets and Fufang Danshen tablet was 0.79% and 0.80%, respectively. Its in vitro dissolution was nearly 70% within 12 h in Fufang Danshen intestinal adhesion pellets, and in Fufang Danshen tablet, the dissolution was about 60% within 20 min and more than 90% within 40 min, and in artificial gastric juice, was less than 20% within 40 min but more than 80% till 150 min. Research suggests that in comparison with Fufang Danshen tablet, in vitro dissolution of borneol in the Fufang Danshen intestinal adhesion pellets showed an obvious sustained release behavior. The borneol in Fufang Danshen intestinal adhesion pellets was included with β-CD and prepared enteric preparations. To some extent, the stimulation on stomach and intestinal mucosa can be reduced and safety can be improved.
Full Text Available Antihistamines Loratadin available in tablet form, as loratadin tablets innovator, branded generic preparations. Socializing generic drugs need information about quality of these drugs, to ensure that the quality of generic drugs not lower or similar to its innovator drugs. The impact of economic crisis caused the price of very expensive drugs. The information quality of generic drugs is expected to increase the use of generic drugs by health practitioners and public. It is necessary for the laboratory data that are qualityparameters, such as dissolution profiles, dissolution testing and determinationof drug dosage levels. Dissolution test method anddetermination of levelsconducted in accordanceto the requirements of the USP (United State of Pharmacopeia. Loratadin dissolution test resultsof tablets A, B and Cin accordancewith the requirements of the USP. Loratadin contentin tablet Ais 103, 73%, B=99,62% and C=100,21%. Loratadin levels in all of these tablets meet the requirements of the USP. Key words: innovator,branded generic drug, dissolution, content
Yassin, Samy; Goodwin, Daniel J; Anderson, Andrew; Sibik, Juraj; Ian Wilson, D; Gladden, Lynn F; Axel Zeitler, J
Disintegration performance was measured by analysing both water ingress and tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from pure MCC with porosities of 10% and 15% showed similar swelling and transport kinetics: within the first 15s, tablets had swollen by up to 33% of their original thickness and water had fully penetrated the tablet following Darcy flow kinetics. In contrast, MCC tablets with a porosity of 5% exhibited much slower transport kinetics, with swelling to only 17% of their original thickness and full water penetration reached after 100s, dominated by case II transport kinetics. The effect of adding superdisintegrant to the formulation and varying the temperature of the dissolution medium between 20°C and 37°C on the swelling and transport process was quantified. We have demonstrated that TPI can be used to non-invasively analyse the complex disintegration kinetics of formulations that take place on timescales of seconds and is a promising tool to better understand the effect of dosage form microstructure on its performance. By relating immediate-release formulations to mathematical models used to describe controlled release formulations, it becomes possible to use this data for formulation design. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3440-3450, 2015. Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.
LUCIANA CATIA BLOCK
Full Text Available Metformin hydrochloride (MH is an oral hypoglycemic agent and a high-dose drug that has poor flow and compression properties. In this study, the feasibility of developing adequate, low cost 500mg tablets of metformin hydrochloride by wet granulation was tested with several binders (Starch / PVP K30®; Starch 1500® /PVP K30®, PVP K30® and PVP K90® in a simple tablet press of the type used in small pharmaceutical laboratories. The drug powder was tested for ability to flow, by determining Carr’s Index (CI and the Hausner ratio (HR. Differential scanning calorimetry and thermogravimetric analysis were carried out on isolated MH and 1:1 (w/w binary mixtures with the excipients. The size distribution, friability, flow properties and drug content of the granules were analyzed, as were the hardness, friability, disintegration, dissolution and uniformity of the dosage form. The drug powder showed CI > 22% and HR > 1.25, characteristic of a poor flow powder, and no significant incompatibilities with the excipients. All the granules showed adequate flow properties and were suitable for pressing into tablets, all of which complied with pharmacopeial specifications. The starch /PVP K30® and starch 1500® /PVP K30® mixtures were best for producing 500 mg MH tablets. Keywords: Metformin hydrochloride. Tablets. Wet granulation. Binders.
Nguyen, Chien; Christensen, J Mark; Ayres, James W
A promising glipizide formulation comprising compression of four-layer coated beads into tablets was prepared. The tablet offered the advantages of: a two-hour lag time before drug release, retaining sustained release characteristics and providing approximately zero-order drug release. Drug release was nearly independent of paddle speeds of 50 and 100 rpm releasing 80% over 14 h similar to the commercial glipizide osmotic pump tablet during dissolution testing while keeping the benefits of multiparticular dosage forms. The tablets contain beads with four layers: (1) the innermost layer consists of 2.5 g glipizide and 3.75 g solid ethylcellulose (Surelease®) coated onto 71.25 g of sugar beads; (2) next a hardening layer of 5 g of hypromellose; (3) the controlled release layer of 7.5 g of Surelease®:lactose at a solids ratio of 100:7 and (4) an outermost layer of 20 g of lactose:sodium starch glycolate (Explotab®) at a 2:1 ratio. Then, beads were compressed into tablets containing 11 mg of glipizide using 1500 lbs of compression pressure. The dissolution test similarity factor (f2) was above 50 for all test conditions for formulation F13 and Glucotrol® with a high of 69.9. The two Surelease® layers both aid controlling drug release, with the Surelease®-drug layer affecting drug release to a greater extent.
Aitha Vijaya Lakshmi
Full Text Available Introduction: Amiloride chemically, 3,5-diamino-6-chloro-N-(diaminomethylene pyrazine-2-carboxamide. It is used in the management of congestive heart failure, available as Amifru tab, Amimide. It causes adverse effects like Nausea, diarrhea and dizziness. Materials: 0.1 N Hydrochloric acid, 0.1 N Sodium hydroxide and 1 mg/ml amiloride drug solution were required. Spectral and absorbance measurements were made using ELICO UV-160 double beam Spectrophotometer. Method: Amiloride drug solution concentration range of 25 to 125ug/ml in 0.1N HCl medium was scanned over the wave length range of 235-320 against blank prepared in 0.1N NaOH solution. Two wavelengths are selected one at positive peak 245 nm and another at negative peak 290 nm, the amplitude is calculated from these values. Results and Discussion: The sum of the absolute values at these wavelengths is called amplitude. The amplitude is proportional to the amount of drug. High accuracy, reproducibility and low t-values were reported from the calibration curve plotted with the amplitude verses amount of drug. So the proposed method is simple, less time consuming and it can be successfully adopted for the estimation of amiloride.
Faisalabad, 5Punjab Forensic Science Agency, Toxicology Unit, Lahore, Pakistan, 6Faculty of Pharmacy University of. Sargodha, Sargodha, Pakistan, 7Faculty of Pharmacy University of Central Punjab, Lahore, Pakistan. *For correspondence: Email: email@example.com; Tel: +92-3006095928. Received: 2 October ...
Various precompression studies were carried out to determine Hausner's ratio, Carr's index, angle of repose, bulk density and tapped density Differential scanning calorimetry (DSC) studies and also post-compression studies to evaluate hardness, friability, weight variation, drug content, in-vitro drug release were conducted ...
Taylor, Michael; Elhissi, Abdelbary M A
The formulation of a new tablet is a time-consuming activity involving the preparation and testing of many different formulations with the aim of identifying one with the desired properties. In complex formulations it may not be clear which excipient is responsible for eliciting a particular property. To investigate partial least squares (PLS) regression analysis of ATR-FTIR spectra of tablets as a predictive and investigative tool in the formulation of novel tablet formulations. Magnesium stearate, lactose, acetylsalicylic acid and Ac-Di-Sol. ATR-FTIR spectra of a simple aspirin tablet formulation with varying amounts of the lubricant magnesium stearate were obtained. PLS models were built using the spectral data as the multivariate variable and various physical properties of the tablets as the univariate variables. PLS models that allowed good predications to be made for samples not included in the training set were obtained for tablet hardness and disintegration time. It was clear from PLS model regression coefficients that magnesium stearate was responsible for the variation in the tablets' physical properties. PLS regression in combination with ATR-FTIR spectroscopy has been shown to be a useful approach for the prediction of the physical properties of tablets.
Guilherme Neves Ferreira
Full Text Available Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed.
Full Text Available The incidence of malaria in Indonesia is about two million cases annually. Dihydroartemisinin-piperaquine (DHP is the first line therapy recommended for uncomplicated malaria treatment, whereas DHP is still fully imported. The generic DHP tablet formulation has the potential to become the first of DHP drug which is locally produced. This study is aimed to formulate generic DHP film coated tablets for antimalaria drug. Tablets were compressed with the combination of wet granulation for piperaquine phosphate (PQP and direct compression method for DHA and coated with a moisture barier coating material. The parameters to evaluate the quality of DHP tablets are physical properties, assay, and dissolution test. DHA and PQP assay were performed by HPLC method. The dissolution testing was conducted by in house method using HCl 0.1 N medium. The result shows physical properties of film-coated tablets meet the requirement, i.e. uniform weight, 7.0-8.5 kp hardness, 0.02% friability and 3 minute 22 seconds disintegration. The assay to determine DHA in tablet was 95.17% and PQP was 97.05%. The result of dissolution testing shows the content of DHA and PQP in the tablet were 113.51% and 96.55%, respesctively. The formulation which is developed meets the general requirement of API in tablet 90–110% and dissolution requirement >75%.
Simonson, Larry A.
This experiment introduces the concept of gravimetric dilutions in the context of tablet analysis. Caffeine tablets are analyzed by absorbance at 274 nm with reference to a standard calibration graph and tested for compliance with the USP criterion. All samples and standards are prepared using gravimetric dilutions without reference to volume or density. This experiment is appropriate for high school and college freshman chemistry courses and may be useful at higher levels. It is only necessary that students have had exposure to Beer's law.
Neumann, Michelle M.; Neumann, David L.
The use of touch screen tablets by young children is increasing in the home and in early childhood settings. The simple tactile interface and finger-based operating features of tablets may facilitate preschoolers' use of tablet application software and support their educational development in domains such as literacy. This article reviews…
Background: Release-retarding polymers in matrix tablets play a vital role in controlling drug release from tablets. Objectives: To prepare metoprolol succinate tablets by direct compression using Ofada rice (Oryza glaberrima Steud) starch acetate, degree of substitution (DS) 2.22, as a matrix for sustained release. Materials ...
Gong, Sheng-Ju; Sun, Shi-Xuan; Sun, Qing-Shen; Wang, Jin-Ye; Liu, Xin-Ming; Liu, Guo-Yan
In our previous study, we reported a novel tablet based on compressed zein microspheres as a universal drug delivery system using the hydrophobic protein zein, which shows zero-order release in the presence of pepsin. However, this formulation had difficulty with disintegration under physiological conditions within 48 h, and thus could not be used directly for oral administration. In the present study, a formulation of ivermectin (IVM) tablets based on compressed zein microspheres was improved as a new dosage form. The plasma disposition pharmacokinetics of IVM tablets based on compressed zein microspheres after oral administration was studied over a 7-day period with six dogs (Canis familiaris), using a commercial IVM tablet (5 mg/piece, Yilijia(®) ) as a control. Clinical efficacy was tested using 270 dogs presented as veterinary patients for the treatment of demodicidosis. A formulation with disintegration time within 15 min could be obtained. The acquired C( max), T(max), and AUC were 9.89 ± 0.34 ng/mL, 11.33 ± 2.63 h, and 883.87 ng h/mL for IVM tablets based on compressed zein microspheres and 9.64 ± 1.05 ng/mL, 7.26 ± 2.09 h, and 666.30 ng h/mL for Yilijia(®), respectively. The bioavailability of the tablets based on compressed zein microspheres was 132.65% that of Yilijia( ®). Efficacy for the dogs in all the IVM tablets based on compressed zein microspheres-treated groups reached 100% at 7, 14, and 21 days post administration.
Full Text Available Orally disintegrating tablets and oral lyophilisates are novel attractive dosage forms that disintegrate or dissolve in the buccal cavity within seconds without necessity of drinking. The major limitation in designing of these dosage forms is unpleasant taste of the drug substance. Cetirizine dihydrochloride is a H1-antihistamine substance indicated for the treatment of allergy. It is characterized by extremely bitter taste, therefore in order to deliver cetirizine dihydrochloride using orodispersible formulations, effective taste-masking is required. The aim of this study was to investigate whether microparticles containing cetirizine dihydrochloride could be successfully used to formulate orally disintegrating tablets by direct compression method and oral lyophilisates by freeze-drying process. Taste masking of cetirizine dihydrochloride was achieved by the spray-drying technique using Eudragit® E PO as the drug agent carrier. Based on the preliminary studies, optimal compositions of microparticles, tablets and lyophilisates were chosen. Obtained dosage forms were characterized for drug content, disintegration time and mechanical properties. In order to determine whether the microparticles subjected to direct compression and freeze-drying process effectively mask the bitter taste of cetirizine dihydrochloride, the in vivo and in vitro evaluation was performed. The results showed that designed formulates with microparticles containing cetirizine dihydrochloride were characterized by appropriate mechanical properties, uniformity of weight and thickness, short disintegration time, and the uniform content of the drug substance. Taste-masking assessment performed by three independent methods (e-tongue evaluation, human test panel and the in vitro drug release revealed that microparticles with Eudragit® E PO are effective taste – masking carriers of cetirizine dihydrochloride and might be used to formulate orally disintegrating tablets and oral
Kaul, Goldi; Huang, Jun; Chatlapalli, Ramarao; Ghosh, Krishnendu; Nagi, Arwinder
The role of poloxamer 188, water and binder addition rate, on retarding dissolution in immediate-release tablets of a model drug from BCS class II was investigated by means of multivariate data analysis (MVDA) combined with design of experiments (DOE). While the DOE analysis yielded important clues into the cause-and-effect relationship between the responses and design factors, multivariate data analysis of the 40+ variables provided additional information on slowdown in tablet dissolution. A steep dependence of both tablet dissolution and disintegration on the poloxamer and less so on other design variables was observed. Poloxamer was found to increase dissolution rates in granules as expected of surfactants in general but retard dissolution in tablets. The unexpected effect of poloxamer in tablets was accompanied by an increase in tablet-disintegration-time-mediated slowdown of tablet dissolution and by a surrogate binding effect of poloxamer at higher concentrations. It was additionally realized through MVDA that poloxamer in tablets either acts as a binder by itself or promotes binder action of the binder povidone resulting in increased intragranular cohesion. Additionally, poloxamer was found to mediate tablet dissolution on stability as well. In contrast to tablet dissolution at release (time zero), poloxamer appeared to increase tablet dissolution in a concentration-dependent manner on accelerated open-dish stability. Substituting polysorbate 80 as an alternate surfactant in place of poloxamer in the formulation was found to stabilize tablet dissolution.
Çelik, Burak; Özdemir, Samet; Barla Demirkoz, Aslı; Üner, Melike
The aim of this study was optimization of buccal piribedil (PR) mucoadhesive tablets to improve its low bioavailability and provide controlled release for the treatment of Parkinson's disease. Buccal tablets were prepared by direct compression method using carbomer (CP), carboxymethyl cellulose (CMC), and hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Physical properties of powder mixtures and buccal tablets were evaluated. Physicochemical compatibility between ingredients was investigated with infrared spectroscopy and differential scanning calorimetry analysis. In vitro dissolution profiles and drug release kinetics of buccal tablets were investigated. Mucoadhesion and ex vivo permeation studies were performed using sheep buccal mucosa. Powder mixtures demonstrated sufficient flow properties and physical characteristics of all tablet formulations were within compendia limits. Tablet ingredients were absent of any chemical interactions. CP tablets displayed slower drug release compared to HPMC tablets with zero order release, while CMC tablets lost their integrity and released entire drug after 6 h following Higuchi model. All formulations displayed adequate mucoadhesion and steady state flux of PR through buccal mucosa were higher with HPMC compared to CP-containing tablets. Overall, HPMC was found to combine desired controlled release and mucoadhesion characteristics with sufficient pharmaceutical quality for optimization of buccal tablets. Piribedil mucoadhesive buccal tablets designed for the first time may introduce a new alternative for the treatment of Parkinson's disease.
Maurer, Jacoba M.; Schellekens, Reinout C. A.; van Rieke, Helen M.; Wanke, Christoph; Iordanov, Ventzeslav; Stellaard, Frans; Wutzke, Klaus D.; Dijkstra, Gerard; van der Zee, Margot; Woerdenbag, Herman J.; Frijlink, Henderik W.; Kosterink, Jos G. W.
Introduction ColoPulse tablets are an innovative development in the field of oral dosage forms characterized by a distal ileum and colon-specific release. Previous studies in humans showed release in the ileo-colonic region, but the relationship between gastrointestinal pH and release was not
Maurer, J.M.; Schellekens, R.C.A.; Van Rieke, H.M.; Stellaard, F.; Wutzke, K.D.; Buurman, D.J.; Dijkstra, G.; Woerdenbag, H.J.; Frijlink, H.W.; Kosterink, J.G.W.
ColoPulse tablets are an innovative development in the field of oral drug delivery and are characterized by a colon-specific release. Until now ColoPulse dosage forms (only capsules) have been studied in healthy volunteers having a standardized breakfast three hours after administration but not in
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Cloxacillin intramammary dosage forms. 526.464... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.464 Cloxacillin intramammary dosage forms. ...
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin intramammary dosage forms. 526.1696... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.1696 Penicillin intramammary dosage forms. ...
Ohrem, H Leonhard; Schornick, Eva; Kalivoda, Adela; Ognibene, Roberto
Various fillers/binders which are applied for the formulation of solid oral dosage forms are assessed for their benefits and drawbacks, including lactose, sorbitol, mannitol, microcrystalline cellulose and calcium hydrogen phosphate dihydrate. A focus of this work was to evaluate the application of mannitol in comparison to other common fillers/binders as it was observed that this excipient is gaining more and more attention in pharmaceutical formulation development and production. While one of the main advantages of conventional fillers/binders such as lactose, microcrystalline cellulose and calcium hydrogen phosphate dihydrate is their low price level, mannitol excels regarding its physicochemical characteristics such as a low hygroscopicity, a strong inertness towards both the API and the patient's body, its good compactibility and the ability to produce extremely robust tablets. Additionally, the suitability of mannitol for the emerging formulation technology of orally disintegrating tablets is pointed out. In summary, it is emphasized that the selection of the filler/binder is highly individual, depending, for example, on the preferred characteristics of the final solid dosage form, the applied API and the available budget. However, mannitol exhibits many strong advantages which can be expected to result in a more widespread application in the near future.
This paper presents understandings of learning in schools where Internet-enabled Information and Communication Technologies (ICTs) are taken for granted. The context is a full-scale 1:1 tablet project in Danish municipality schools where this study bring forward expressions of learning from one class (12-13 year old children) in order to offer…
Bi, Mingda; Kyad, Ali; Alvarez-Nunez, Fernando; Alvarez, Francisco
Enhancing and sustaining AMG 009 dissolution from a matrix tablet via microenvironmental pH modulation and supersaturation, where poorly soluble acidic AMG 009 molecule was intimately mixed and compressed together with a basic pH modifier (e.g., sodium carbonate) and nucleation inhibitor hydroxypropyl methylcellulose K100 LV (HPMC K100 LV), was demonstrated previously. However, not all acidic or basic drugs are compatible with basic or acidic pH modifiers either chemically or physically. The objective of this study is to investigate whether similar dissolution enhancement of AMG 009 can be achieved from a bilayer dosage form, where AMG 009 and sodium carbonate are placed in a separate layer with or without the addition of HPMC K100 LV in each layer. Study results indicate that HPMC K100 LV-containing bilayer dosage forms gained similar dissolution enhancement as matrix dosage forms did. Bilayer dosage forms without HPMC K100 LV benefitted the least from dissolution enhancement.
Full Text Available The dosage compensation complex (DCC in Drosophila melanogaster is responsible for up-regulating transcription from the single male X chromosome to equal the transcription from the two X chromosomes in females. Visualization of the DCC, a large ribonucleoprotein complex, on male larval polytene chromosomes reveals that the complex binds selectively to many interbands on the X chromosome. The targeting of the DCC is thought to be in part determined by DNA sequences that are enriched on the X. So far, lack of knowledge about DCC binding sites has prevented the identification of sequence determinants. Only three binding sites have been identified to date, but analysis of their DNA sequence did not allow the prediction of further binding sites. We have used chromatin immunoprecipitation to identify a number of new DCC binding fragments and characterized them in vivo by visualizing DCC binding to autosomal insertions of these fragments, and we have demonstrated that they possess a wide range of potential to recruit the DCC. By varying the in vivo concentration of the DCC, we provide evidence that this range of recruitment potential is due to differences in affinity of the complex to these sites. We were also able to establish that DCC binding to ectopic high-affinity sites can allow nearby low-affinity sites to recruit the complex. Using the sequences of the newly identified and previously characterized binding fragments, we have uncovered a number of short sequence motifs, which in combination may contribute to DCC recruitment. Our findings suggest that the DCC is recruited to the X via a number of binding sites of decreasing affinities, and that the presence of high- and moderate-affinity sites on the X may ensure that lower-affinity sites are occupied in a context-dependent manner. Our bioinformatics analysis suggests that DCC binding sites may be composed of variable combinations of degenerate motifs.
Efficacy of a single dose of milbemycin oxime/praziquantel combination tablets, Milpro(®), against adult Echinococcus multilocularis in dogs and both adult and immature E. multilocularis in young cats.
Cvejic, Dejan; Schneider, Claudia; Fourie, Josephus; de Vos, Christa; Bonneau, Stephane; Bernachon, Natalia; Hellmann, Klaus
Two single-site, laboratory, negatively controlled, masked, randomised dose confirmation studies were performed: one in dogs, the other in cats. After a period of acclimatisation, both the dogs and cats were orally infected with Echinococcus multilocularis protoscoleces. In the dog study, 10 dogs received a single dose of Milpro® tablets at a minimum dose of 0.5 mg/kg milbemycin oxime and 5 mg/kg praziquantel 18 days post-infection and 10 dogs received no treatment. In the cat study, 10 cats received a single dose of Milpro® tablets at a minimum dose of 2 mg/kg milbemycin oxime and 5 mg/kg praziquantel 7 days post-infection, 10 cats received a single dose of the treatment 18 days post-infection and 10 cats remained untreated. In both studies, intestinal worm counts were performed 23 days post-infection at necropsy. No worms were retrieved from any of the 30 treated animals. Nine of 10 control dogs had multiple worms (geometric mean 91, arithmetic mean 304) and all 10 control cats had multiple worms (geometric mean 216, arithmetic mean 481). The difference in worm counts between all three treated groups and their controls was highly significant (ANOVA p values of log transformed data dogs and cats as well as for elimination of immature E. multilocularis in cats as evidenced by the effectiveness of treatment 7 days post-infection. The treatments were well accepted and tolerated, and there were no adverse drug reactions observed.
Zargaran, Arman; Zarshenas, Mohammad M; Hosseinkhani, Ayda; Mehdizadeh, Alireza
Medical sciences including pharmacy flourished in Persia throughout medieval times. The oldest pharmacopeias which discussed pharmaceutical formulations were created by them, called Qarabadin. Among various dosage forms which were described, Jawarish was a gastrointestinal dosage form which was made from different ingredients for different purposes such as stomach tonic, digestive, carminative, laxative, astringent, visceral analgesic, antihaemorrhoid, antiemetic, emetic, antireflux and anticolic. This paper, introduces their preparation, general considerations and five common examples of Jawarish.
Gaikwad, Vinay Dhananjay; Yadav, Vishal Dadasaheb; Gaikwad, Manish Dhananjay
Introduction: The present study aims at developing a gastroretentive swellable and floating matrix tablet formulation of ciprofloxacin hydrochloride (HCl) for the effective treatment of infections caused by susceptible organisms. Ciprofloxacin HCl is a fluoroquinoline antibiotic drug. Ciprofloxacin HCl is more stable in acidic medium and it has a narrow absorption window which is sited at the stomach and proximal portions of the small intestine, so it covers the required criteria for selection of drug for gastroretentive dosage form. Materials and Methods: Ciprofloxacin HCl gastroretentive tablets were formulated by using direct compression method and different grades of hydroxypropyl methylcellulose as suspending and stabilizing agent (polymer), sodium starch glycolate (SSG), crospovidone as disintegrates, sodium bicarbonate as alkalizing agent and magnesium stearate as lubricant. Results: The tablets were evaluated for post compression parameters. All the parameters were within the pharmacopoeial limits. Conclusion: The in vitro dissolution studies showed that the drug release was fast in formulations F2, F4 and F6 containing SSG as super disintegrant when compared with all other formulations. In SEM study of F2 formulation shows maximum swelling and porosity observed after 12 h. Hence, formulation F2 shows the best formulation among the six formulations containing different binders and super disintegrants. PMID:25006553
Choi, H.C.; Kang, S.J.; Youn, M.O.; Lee, S.J.; Kim, H.J.; Kim, J.Y. [Korea Food and Drug Administration, Seoul (Korea); Cha, K.W. [Inha University, Inchon (Korea)
A rapid and simple determination of diazepam in intact diazepam tablets has been investigated using the near infrared spectroscopy(NIRS) combined with partial least squares regression. The separate calibration curves of 2 mg and 5 mg diazepam tablets were studied, as well as the linearity, concentration range and reproducibility of those calibration curves were evaluated. The correlation coefficients of calibration curves of 2 mg and 5 mg diazepam tablets are 0.99416 and 0.9159, respectively and the standard errors of calibration curves(SEC) are 0.018% and 0.032%, respectively. (author). 13 refs., 4 tabs., 4 figs.
Full Text Available A rapid, highly sensitive high performance liquid chromatographic method has been developed for the determination of finasteride(FNS in bulk drug and in tablets. FNS was eluted from a ODS C18 reversed phase column at laboratory temperature (30 ± 2°C with a mobile phase consisting of methanol and water (80+20 at a flow rate of 1 mL min-1 with UV detection at 225 nm. The retention time was ∼ 6.1 min and each analysis took not more than 10 min. Quantitation was achieved by measurement of peak area without using any internal standard. Calibration graph was linear from 2.0 to 30 μg mL-1 with limits of detection (LOD and quantification (LOQ being 0.2 and 0.6 μg mL-1, respectively. The method was validated according to the current ICH guidelines. Within-day co efficients of variation (CV ranged from 0.31 to 0.69% and between-day CV were in the range 1.2-3.2%. Recovery of FNS from the pharmaceutical dosage forms ranged from 97.89 – 102.9 with CV of 1.41-4.13%. The developed method was compared with the official method for FNS determination in its tablet forms.
Sagar Suman Panda
Full Text Available Aim: The present work deals with development and validation of a novel, precise, and accurate spectrophotometric method for the estimation of citicoline sodium (CTS in tablets. This spectrophotometric method is based on the principle that CTS shows two different forms that differs in the absorption spectra in basic and acidic medium. Materials and Methods: The present work was being carried out on Shimadzu 1800 Double Beam UV-visible spectrophotometer. Difference spectra were generated using 10 mm quartz cells over the range of 200-400 nm. Solvents used were 0.1 M NaOH and 0.1 M HCl. Results: The maxima and minima in the difference spectra of CTS were found to be 239 nm and 283 nm, respectively. Amplitude was calculated from the maxima and minima of spectrum. The drug follows linearity in the range of 1-50 μ/ml (R 2 = 0.999. The average % recovery from the tablet formulation was found to be 98.47%. The method was validated as per International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use: ICH Q2(R1 Validation of Analytical Procedures: Text and Methodology guidelines. Conclusion: This method is simple and inexpensive. Hence it can be applied for determination of the drug in pharmaceutical dosage forms.
Azad, Mohammad A; Osorio, Juan G; Brancazio, David; Hammersmith, Gregory; Klee, David M; Rapp, Kersten; Myerson, Allan
Due to the complex nature of the pharmaceutical supply chain, the industry faces several major challenges when it comes to ensuring an adequate supply of quality drug products. These challenges are not only the causes of supply chain disruptions and financial loss, but can also prevent underserved and remote areas from receiving life-saving drugs. As a preliminary demonstration to mitigate all these challenges, at MIT we have developed active pharmaceutical ingredients manufacturing in a miniature platform. However, manufacturing of final oral solid dosage as tablets from drug substances had not been demonstrated. In this study, a compact, portable, re-configurable, and automated tablet manufacturing system, roughly the size of a North American household oven, [72.4 cm (length) × 53.3 cm (width) × 134.6 cm (height)] was designed, built and demonstrated. This miniature system is able to manufacture on-demand tablets from drug crystals on a scale of hundreds to thousands per day. Ibuprofen and Diazepam, each having different drug loading, were manufactured using this miniature system and meet U.S. Pharmacopeia standards. We foresee this flexible, miniature, plug-and-play pharmaceutical solids dosage manufacturing system advancing on-demand ready-to-use pharmaceuticals enabling future treatment of human diseases at the point-of-care. Copyright © 2018 Elsevier B.V. All rights reserved.
Punyamurthula, Nagendra S; Hingorani, Tushar; Adelli, Goutham; Gul, Waseem; ElSohly, Mahmoud A; Repka, Michael A; Majumdar, Soumyajit
Cannabinoids are increasingly being used in the treatment of chemotherapy-induced nausea and vomiting (CINV) because of their action on the cannabinoid receptors, CB1 and CB2. The currently marketed capsule formulations (sesame oil based and crystalline powder) are required to be administered frequently to maintain therapeutic levels, which leads to non-compliance. In the present study, oral controlled release tablet formulations of Δ(9)-tetrahydrocannabinol (THC) were prepared using the lipids Precirol® and Compritol®. Release profiles using THC-lipid matrices and/or with the lipids in the external phase (blend) were evaluated. The effect of directly compressible diluents lactose mixture (Ludipress®), dicalcium phosphate anhydrous (Emcompress®) and microcrystalline cellulose (Avicel® 102) on tablet characteristics and in vitro drug release was also investigated. Further, in vitro THC release in the presence of a lipase inhibitor, Pluronic® F68, was also studied. A 24 h zero-order THC release profile was obtained with a combination of Precirol® and Compritol® in the compression blend. Addition of Pluronic® F68 did not alter THC release in vitro. These optimized tablets were chemically and physically stable for 3 months, the last time point tested, at 25 °C/60% RH. The overall results demonstrate the feasibility of preparing oral THC tablets for once a day administration which can improve CINV management.
Shreeram S Savarikar
Full Text Available Aim of the Study: Development of standardized, synergistic, safe and effective traditional herbal formulations with robust scientific evidence can offer faster and more economical alternatives for the treatment of disease. The main objective was to develop a method of preparation of guggulkalpa tablets so that the tablets meet the criteria of efficacy, stability, and safety. Materials and Methods: Triphalaguggulkalpa tablet, described in sharangdharsanhita and containing guggul and triphala powder, was used as a model drug. Preliminary experiments on marketed triphalaguggulkalpa tablets exhibited delayed in vitro disintegration that indicated probable delayed in vivo disintegration. The study involved preparation of triphalaguggulkalpa tablets by Ayurvedic text methods and by wet granulation, dry granulation, and direct compression method. The tablets were evaluated for loss on drying, volatile oil content, % solubility, and steroidal content. The tablets were evaluated for performance tests like weight variation, disintegration, and hardness. Results: It was observed that triphalaguggulkalpa tablets, prepared by direct compression method, complied with the hardness and disintegration tests, whereas tablets prepared by Ayurvedic text methods failed. Conclusion: Direct compression is the best method of preparing triphalaguggulkalpa tablets.
Ciurba Adriana; Rédai Emőke; Pop Ioana; Antonoaea Paula; Todoran Nicoleta
Objective: The aim of this study is to develop lactose-free orodispersible tablets with loratadine for patients with lactose intolerance. Materials and methods: Seven compositions (F1-F7) of 10 mg loratadine were prepared in form of orally disintegrating tablets, by direct compression, using croscarmellose sodium and pre-gelatinized starch in various concentrations as superdisintegrants, diluted with microcrystalline cellulose and combined with mannitol and maltodextrin as binder agents. The ...
Edinger, Magnus; Bar-Shalom, Daniel; Sandler, Niklas; Rantanen, Jukka; Genina, Natalja
The use of inkjet printing (IJP) technology enables the flexible manufacturing of personalized medicine with the doses tailored for each patient. In this study we demonstrate, for the first time, the applicability of IJP in the production of edible dosage forms in the pattern of a quick response (QR) code. This printed pattern contains the drug itself and encoded information relevant to the patient and/or healthcare professionals. IJP of the active pharmaceutical ingredient (API)-containing ink in the pattern of QR code was performed onto a newly developed porous and flexible, but mechanically stable substrate with a good absorption capacity. The printing did not affect the mechanical properties of the substrate. The actual drug content of the printed dosage forms was in accordance with the encoded drug content. The QR encoded dosage forms had a good print definition without significant edge bleeding. They were readable by a smartphone even after storage in harsh conditions. This approach of efficient data incorporation and data storage combined with the use of smart devices can lead to safer and more patient-friendly drug products in the future. Copyright © 2017 Elsevier B.V. All rights reserved.
Chan, K K; Mojaverian, P; Ziehmer, B A; John, V A
A radiotelemetric technique with the Heidelberg capsule (HC) was used to improve the quality of data generated in a bioavailability study involving an enteric-coated (EC) formulation. Further, changes in plasma levels of the drug from other dosage forms were related to changes in pH environment as determined by the HC. Eight healthy male subjects received the following treatments, 15 min after a light breakfast, according to a randomized, four-way crossover design: (A) HC and 75 mg of a diclofenac sodium aqueous buffered solution: (B) HC and one 75-mg Voltaren EC tablet; (C) HC and one 100-mg Voltaren slow-release (SR) tablet; and (D) HC alone. Each treatment was separated by a 1-week washout period. Two additional subjects subsequently received Treatment B only. Multiple peaks were observed in the drug plasma level-time profiles for the buffered aqueous solution which, in all cases, occurred before gastric emptying of the HC. The multiple peaks were not observed for the Voltaren SR tablet, but a variable absorption lag time occurred which coincided with the gastric residence time of the SR tablet. For the EC tablet the variability of individual plasma level-time profiles was drastically reduced when the time after dosing was adjusted to coincide with gastric emptying of the HC. Finally, the lag time between gastric emptying of the EC tablet and the onset of drug absorption was consistently at 1 hr for all subjects. This lag time was longer than the in vitro disintegration or dissolution times measured under USP conditions.
Mah, Pei T; Novakovic, Dunja; Saarinen, Jukka; Van Landeghem, Stijn; Peltonen, Leena; Laaksonen, Timo; Isomäki, Antti; Strachan, Clare J
To investigate the effect of compression on the crystallization behavior in amorphous tablets using sum frequency generation (SFG) microscopy imaging and more established analytical methods. Tablets containing neat amorphous griseofulvin with/without excipients (silica, hydroxypropyl methylcellulose acetate succinate (HPMCAS), microcrystalline cellulose (MCC) and polyethylene glycol (PEG)) were prepared. They were analyzed upon preparation and storage using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM) and SFG microscopy. Compression-induced crystallization occurred predominantly on the surface of the neat amorphous griseofulvin tablets, with minimal crystallinity being detected in the core of the tablets. The presence of various types of excipients was not able to mitigate the compression-induced surface crystallization of the amorphous griseofulvin tablets. However, the excipients affected the crystallization rate of amorphous griseofulvin in the core of the tablet upon compression and storage. SFG microscopy can be used in combination with ATR-FTIR spectroscopy and SEM to understand the crystallization behaviour of amorphous tablets upon compression and storage. When selecting excipients for amorphous formulations, it is important to consider the effect of the excipients on the physical stability of the amorphous formulations.
Nguyen, Chien; Christensen, J Mark; Ayres, James W
Novel 'beads-in-a-tablet' formulations (total weight ∼740-780 mg) have been prepared that meet USP 31 requirements for Delayed Release of mesalamine. Several methods are presented that overcome breakage of beads during tablet compaction were explored. Bead formulations comprise a combination of extrusion and spheronization to produce a relatively high drug load (80%), followed by coating (25%) with a colonic-targeted drug release polymer (polymethacrylates, Eudragit(®) S100), overcoated (3%) with hydroxypropyl methylcellulose (Opadry(®)) to improve bead binding and compactability, and using 20% coat of lactose/sodium starch glycolate (Explotab(®)) as binder/disintegrant/cushioning agent, thus allowing a sufficiently thick coating to be uniform and without being broken during tablet compaction. Then, the aforementioned beads were compressed into tablets at 1500 pounds of pressure containing 400 mg of mesalamine, and finally coating the compressed tablets with Surelease(®) (ethylcellulose):Opadry(®) = 1:0.5 ranging from 1.5-2.5% weight gain; the resulting tablets met USP 31 dissolution requirements for delayed release tablets.
Badal Tejedor, Maria; Nordgren, Niklas; Schuleit, Michael; Rutland, Mark W; Millqvist-Fureby, Anna
Tablets are the most convenient form for drug administration. However, despite the ease of manufacturing problems such as powder adhesion occur during the production process. This study presents surface and structural characterization of tablets formulated with commonly used excipients (microcrystalline cellulose (MCC), lactose, mannitol, magnesium (Mg) stearate) pressed under different compaction conditions. Tablet surface analyses were performed with scanning electron microscopy (SEM), profilometry and atomic force microscopy (AFM). The mechanical properties of the tablets were evaluated with a tablet hardness test. Local adhesion detected by AFM decreased when Mg stearate was present in the formulation. Moreover, the tablet strength of plastically deformable excipients such as MCC was significantly decreased after addition of Mg stearate. Combined these facts indicate that Mg stearate affects the particle-particle bonding and thus elastic recovery. The MCC excipient also displayed the highest hardness which is characteristic for a highly cohesive material. This is discussed in the view of the relatively high adhesion found between MCC and a hydrophilic probe at the nanoscale using AFM. In contrast, the tablet strength of brittle materials like lactose and mannitol is unaffected by Mg stearate. Thus fracture occurs within the excipient particles and not at particle boundaries, creating new surfaces not previously exposed to Mg stearate. Such uncoated surfaces may well promote adhesive interactions with tools during manufacture. Copyright © 2015 Elsevier B.V. All rights reserved.
Muteki, Koji; Swaminathan, Vidya; Sekulic, Sonja S; Reid, George L
In pharmaceutical tablet manufacturing processes, a major source of disturbance affecting drug product quality is the (lot-to-lot) variability of the incoming raw materials. A novel modeling and process optimization strategy that compensates for raw material variability is presented. The approach involves building partial least squares models that combine raw material attributes and tablet process parameters and relate these to final tablet attributes. The resulting models are used in an optimization framework to then find optimal process parameters which can satisfy all the desired requirements for the final tablet attributes, subject to the incoming raw material lots. In order to de-risk the potential (lot-to-lot) variability of raw materials on the drug product quality, the effect of raw material lot variability on the final tablet attributes was investigated using a raw material database containing a large number of lots. In this way, the raw material variability, optimal process parameter space and tablet attributes are correlated with each other and offer the opportunity of simulating a variety of changes in silico without actually performing experiments. The connectivity obtained between the three sources of variability (materials, parameters, attributes) can be considered a design space consistent with Quality by Design principles, which is defined by the ICH-Q8 guidance (USDA 2006). The effectiveness of the methodologies is illustrated through a common industrial tablet manufacturing case study.
Cohen, N; Golik, A; Dishi, V; Zaidenstein, R; Weissgarten, J; Averbukh, Z; Modai, D
Oral furosemide solution was claimed to produce a greater diuretic response than furosemide tablets in patients with congestive heart failure. The aim of this study was to assess this observation and to further investigate the effects on the electrolyte balance. We compared the effects of oral furosemide in tablets versus oral furosemide solution on serum levels as well as on 4- and cumulative 24-hour urinary volume and sodium, potassium, calcium, magnesium and zinc excretions in 10 patients with moderate congestive heart failure due to ischemic heart disease. Oral furosemide (40-80 mg) was given at the usual once-daily dosage. No change in serum electrolyte levels has been found. All urinary parameters, except zinc, were significantly greater during the first 4 h following oral solution as compared with tablets (volume p electrolytes remained within normal limits at 4 and 24 h.
Hasçiçek, Canan; Yüksel-Tilkan, Günseli; Türkmen, Berna; Ozdemir, Nurten
Floating dosage forms of acetylsalicylic acid, used for its antithrombotic effect, were developed to prolong gastric residence time and increase bioavailability. In the two-layer tablet formulation, hydroxypropyl methylcellulose (HPMC) of high viscosity and an effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained the drug, direct tableting agent and different types of matrix-forming polymers such as HPMC of low viscosity, sodium carboxymethylcellulose and chitosan. Tablets were prepared using a direct compression technique. The effect of formulation variables on physicochemical and floating properties and the drug release from tablets were investigated. Floating ability was dependent on the amount of effervescent agent and gel-forming polymer of the floating layer. Drug release was prolonged to 8 hours by changing the type and viscosity of the matrix-forming polymer in the drug-loading layer and all formulations showed a diffusion release mechanisms.
Sunil, Songa Ambedkar; Srikanth, Meka Venkata; Rao, Nali Sreenivasa; Murthy, Kolapalli Venkata Ramana
As the main intent of delivering maximum concentration of drug available from the dosage form, an oral compression coated tablet (CCT) was intended to develop with a predetermined lag time of 6 hrs before immediate release of drug to target circadian rhythms of rheumatoid arthritis. Solid dispersions are promising approach to enhance drug release, which later will be developed as core tablet formulation and compression coated with polyethylene oxide (PEO WSR 303). Solid dispersions were formulated with different ratio of drug and carrier (sucrose fatty acid esters 1811) using solvent evaporation and melt granulation technique, optimized solid dispersion was formulated as core tablet with different diluents. Optimized core tablet was compression coated with PEO WSR 303 along with a channeling agent (DCL 21, mannitol, HPMC 5 cps and starch 1500). Lag time before immediate release of drug was markedly dependent on weight ratios of polymer and channeling agent used, which ranged from 4 to 12 hrs. Optimized solid dispersion (S9) was used for formulating optimized core tablet formulation (C8). CCT (T8) prepared with core tablet (C8) along with mannitol provided a lag time of 6 hrs with minimum concentration of channeling agent used, which was also supported from the permeability study results. Incompatibility and characterization was confirmed from DSC, XRD, FTIR and SEM studies. Unaltered Cmax and AUC0-t but delayed Tmax following oral ingestion of optimized formulation (T8) to human volunteers indicated clear lag time before immediate release of drug, which is suitable for treating rheumatoid arthritis following circadian rhythm.
Diós, Péter; Szigeti, Krisztián; Budán, Ferenc; Pócsik, Márta; Veres, Dániel S; Máthé, Domokos; Pál, Szilárd; Dévay, Attila; Nagy, Sándor
The objective of the study was to reveal the influence of necessarily added barium sulfate (BaSO4) X-ray contrast material on floating drug delivery tablets. Based on literature survey, a chosen floating tablet composition was determined containing HPMC and carbopol 943P as matrix polymers. One-factor factorial design with five levels was created for evaluation of BaSO4 (X1) effects on experimental parameters of tablets including: floating lag time, total floating time, swelling-, erosion-, dissolution-, release kinetics parameters and X-ray detected volume changes of tablets. Applied concentrations of BaSO4 were between 0 and 20.0% resulting in remarkable alteration of experimental parameters related especially to flotation. Drastic deterioration of floating lag time and total floating time could be observed above 15.0% BaSO4. Furthermore, BaSO4 showed to increase the integrity of tablet matrix by reducing eroding properties. A novel evaluation of dissolutions from floating drug delivery systems was introduced, which could assess the quantity of drug dissolved from dosage form in floating state. In the cases of tablets containing 20.0% BaSO4, only the 40% of total API amount could be dissolved in floating state. In vitro fine resolution X-ray CT imagings were performed to study the volume change and the voxel distributions as a function of HU attenuations by histogram analysis of the images. X-ray detected relative volume change results did not show significant difference between samples. After 24h, all tablets containing BaSO4 could be segmented, which highlighted the fact that enough BaSO4 remained in the tablets for their identification. Copyright Â© 2016 Elsevier B.V. All rights reserved.
Jorge Enrique Rodríguez Chanfrau
Full Text Available Introduction: Raloxifene is a selective estrogen receptor modulator from the benzothiophene family. Several clinical trials have shown that raloxifene reduces bone loss rate in the spinal column and may increase bone mass at certain sites. Objective: to determine the physical and chemical stabilities of raloxifene tablets. Methods. three pilot scale batches of 5 kg each were prepared. In vitro dissolution, chemical stability, photostability and humidity studies were carried out. Samples were collected at 0, 1, 2, 3 and 6 months for the accelerated stability study and at 0, 6, 12, 18 and 24 months for the shelf life stability study. Chemical stability was determined using high performance liquid chromatography analytical method, which was developed and validated prior to the study. Results: in the accelerated stability study, the percentages of dissolved drug were more than 90 % and drug content porcentages were between 90 % and 110 %. Humidity conditions affected the chemical stability of the tablets. Conclusions: All raloxifene tablet batches formulations were stable for 24 months in the studied containers stored at 32 ± 2 ºC and waterproof. In vitro drug release dissolution showed good results for 24 months.
Wening, Klaus; Laukamp, Eva Julia; Thommes, Markus; Breitkreutz, Jörg
New devices enabling freely selectable dosing of solid oral medications are urgently needed for personalized medicine. One approach is the use of the recently published Solid Dosage Pen, allowing flexible dosing of tablet-like sustained release slices from drug loaded extruded strands. Slices were suitable for oral single dosed application. The aim of the present study was the development of immediate release dosage forms for applications of the device, especially for young children. Using two model drugs, two different concepts were investigated and evaluated. Effervescent formulations were manufactured by an organic wet-extrusion process and immediate release formulations by a melt-extrusion process. Dissolution experiments were performed for both formulations to ensure the immediate release behavior. Extruded strands were individually dosed by the Solid Dosage Pen. Various doses of the two formulations were analyzed regarding uniformity of mass and content according to pharmacopoeial specifications. Proof of concept was demonstrated in both approaches as results comply with the regulatory requirements. Furthermore, storing stress tests were performed and drug formulations were characterized after storing. The results show that suitable packaging material has been selected and storage stability is probable. PMID:25562361
Debotton, Nir; Dahan, Arik
Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the "magic bullets" concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration. When formulating challenging molecules into solid oral dosage forms, polymeric pharmaceutical excipients permit masking undesired physicochemical properties of drugs and consequently, altering their pharmacokinetic profiles to improve the therapeutic effect. As a result, the number of synthetic and natural polymers available commercially as pharmaceutical excipients has increased dramatically, offering potential solutions to various difficulties. For instance, the different polymers may allow increased solubility, swellability, viscosity, biodegradability, advanced coatings, pH dependency, mucodhesion, and inhibition of crystallization. The aim of this article is to provide a wide angle prospect of the different uses of pharmaceutical polymers in solid oral dosage forms. The various types of polymeric excipients are presented, and their distinctive role in oral drug delivery is emphasized. The comprehensive know-how provided in this article may allow scientists to use these polymeric excipients rationally, to fully exploit their different features and potential influence on drug delivery, with the overall aim of making better drug products. © 2016 Wiley Periodicals, Inc.
Full Text Available A novel approach was carried out to develop and validate a rapid, specific, accurate and precise reverse phase ultra performance liquid chromatographic (UPLC method for the simultaneous separation and quantification of secnidazole, fluconazole and azithromycin in pharmaceutical dosage forms. The developed analytical method is superior in technology to conventional HPLC with respect to time, resolution, solvent consumption and cost of analysis. Elution time for the separation was 10 min and ultra violet detection was carried out at 210 nm. Efficient separation was achieved on BEH C18 sub-2-μm UPLC column using 0.002 M Na2HPO4 and acetonitrile as organic solvent in a gradient program. Benzophenone was used as internal standard. Resolutions between secnidazole, fluconazole and azithromycin were found to be more than 4.8. The calibration graphs were linear for secnidazole, fluconazole, benzophenone and azithromycin. The method showed excellent recoveries for all dosage forms. The test solution was found to be stable in diluent for 72 h when stored in the refrigerator between 2 to 8 °C. The proposed UPLC method was validated with respect to linearity, accuracy, precision, specificity and robustness and can be used for the simultaneous estimation of secnidazole, fluconazole and azithromycin in tablet dosage forms available as a combi kit.
Szymańska, Emilia; Winnicka, Katarzyna; Amelian, Aleksandra; Cwalina, Urszula
Topical administration of clotrimazole represents the common use therapy in the antimycotic genitourinary tract treatment. Due to the fast self-cleaning action of the vagina, commercially available vaginal dosage forms with clotrimazole cannot assure prolonged contact time with mucosa, therefore the main objective of this study was to develop a dosage form for vaginal administration of clotrimazole using chitosan-a biodegradable and biocompatible derivative of chitin. Tablets mucoadhesive properties were examined using texture analyser under the presence of porcine vaginal mucosa and two different models of adhesive layers- mucin gel and gelatine discs. In addition, friability, hardness, swelling behaviour, residence time, surface morphology of the performed tablets, the in vitro release profile of clotrimazole and clotrimazole release kinetics were determined. The release of clotrimazole from formulations with 25 or 40% of chitosan (F2 and F3) followed non Fickian diffusion through chitosan-gel layer and was retarded up to 6 h. Additionally, tablets F2 showed the best results in terms of mucoadhesive properties and appeared to be a good alternative to commercially available antimycotic vaginal dosage forms.
Richey, Roberta H; Hughes, Clare; Craig, Jean V; Shah, Utpal U; Ford, James L; Barker, Catrin E; Peak, Matthew; Nunn, Anthony J; Turner, Mark A
This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same
Wilson, C G; Clarke, Cyril P; Starkey, Yan Yan L; Clarke, Geoffrey D
Acetaminophen (paracetamol, APAP) is widely used to relieve mild-to-moderate pain and reduce fever. Absorption of the drug can be impacted by dosage form; this may have implications for pain relief in some individuals, potentially accounting for suboptimal efficacy in analgesia. To assess the disintegration and dissolution of a new fast-dissolving acetaminophen tablet formulation (FD-APAP) and the impact on pharmacokinetic and pharmacodynamic parameters. Two randomized, single-center, open-label, single-dose, two-way crossover studies in healthy subjects to compare FD-APAP (2 × 500 mg tablets) with standard acetaminophen (2 × 500 mg tablets). Gamma scintigraphy was used to assess tablet disintegration (Study 1, N = 24), and plasma profiles were evaluated in the fasted state (Study 2, N = 40). In Study 1, the mean time to complete disintegration (12.9 vs. 69.6 min, P < 0.0001) and onset of disintegration were both significantly faster with FD-APAP than with standard acetaminophen (P < 0.0001). For Study 2, median T(max) was significantly faster for FD-APAP (0.50 vs. 0.67 h, P < 0.01) and AUC(0-30 min) was significantly greater (4.51 vs. 2.74, P < 0.05). AUC(0-t) and AUC(0-inf) were comparable between the two study treatments. Despite the absence of comparative clinical data, the FD-APAP formulation may be expected to overcome some of the issues associated with the slow and variable absorption of standard acetaminophen tablet formulations, improving therapeutic outcome and avoiding the need to switch to alternative therapeutic options. Compared with standard acetaminophen, the FD-APAP formulation results in significantly faster onset of disintegration and more rapid absorption.
Narayan, Aditee P; Whicker, Shari A; Benjamin, Robert W; Hawley, Jeffrey; McGann, Kathleen A
Learner benefits of tablet computer use have been demonstrated, yet there is little evidence regarding faculty tablet use for teaching. Our study sought to determine if supplying faculty with tablet computers and peer mentoring provided benefits to learners and faculty beyond that of non-tablet-based teaching modalities. We provided faculty with tablet computers and three 2-hour peer-mentoring workshops on tablet-based teaching. Faculty used tablets to teach, in addition to their current, non-tablet-based methods. Presurveys, postsurveys, and monthly faculty surveys assessed feasibility, utilization, and comparisons to current modalities. Learner surveys assessed perceived effectiveness and comparisons to current modalities. All feedback received from open-ended questions was reviewed by the authors and organized into categories. Of 15 eligible faculty, 14 participated. Each participant attended at least 2 of the 3 workshops, with 10 to 12 participants at each workshop. All participants found the workshops useful, and reported that the new tablet-based teaching modality added value beyond that of current teaching methods. Respondents developed the following tablet-based outputs: presentations, photo galleries, evaluation tools, and online modules. Of the outputs, 60% were used in the ambulatory clinics, 33% in intensive care unit bedside teaching rounds, and 7% in inpatient medical unit bedside teaching rounds. Learners reported that common benefits of tablet computers were: improved access/convenience (41%), improved interactive learning (38%), and improved bedside teaching and patient care (13%). A common barrier faculty identified was inconsistent wireless access (14%), while no barriers were identified by the majority of learners. Providing faculty with tablet computers and having peer-mentoring workshops to discuss their use was feasible and added value.
Nippolainen, Ervin; Ervasti, Tuomas; Ketolainen, Jarkko; Kamshilin, Alexei A.
A multispectral imaging system with computer controlled light source of 16 light emitting diodes is applied for measuring of tablet porosity. The system is based on a subspace vector model of surface reflection. The measured spectral data are compressed on the stage of measurement and used directly for the discrimination of tablets with different porosity. The experimental results demonstrate that the multispectral imaging system is a potential method for tablet porosity measurement.
Lesar, Timothy S
CONTEXT Prescribing errors involving medication dose formulations have been reported to occur frequently in hospitals. No systematic evaluations of the characteristics of errors related to medication dosage formulation have been performed. OBJECTIVE To quantify the characteristics, frequency, and potential adverse patient effects of prescribing errors involving medication dosage forms . DESIGN Evaluation of all detected medication prescribing errors involving or related to medication dosage forms in a 631-bed tertiary care teaching hospital. MAIN OUTCOME MEASURES Type, frequency, and potential for adverse effects of prescribing errors involving or related to medication dosage forms. RESULTS A total of 1,115 clinically significant prescribing errors involving medication dosage forms were detected during the 60-month study period. The annual number of detected errors increased throughout the study period. Detailed analysis of the 402 errors detected during the last 16 months of the study demonstrated the most common errors to be: failure to specify controlled release formulation (total of 280 cases; 69.7%) both when prescribing using the brand name (148 cases; 36.8%) and when prescribing using the generic name (132 cases; 32.8%); and prescribing controlled delivery formulations to be administered per tube (48 cases; 11.9%). The potential for adverse patient outcome was rated as potentially “fatal or severe” in 3 cases (0.7%), and “serious” in 49 cases (12.2%). Errors most commonly involved cardiovascular agents (208 cases; 51.7%). CONCLUSIONS Hospitalized patients are at risk for adverse outcomes due to prescribing errors related to inappropriate use of medication dosage forms. This information should be considered in the development of strategies to prevent adverse patient outcomes resulting from such errors. PMID:12213138
Shahtalebi Mohammad Ali
Full Text Available Introduction: Difficulty in swallowing is common among all age groups, especially elderly and pediatrics. Orally disintegrating tablets may constitute an innovative dosage form that overcome the problem of swallowing and provide a quick onset of action. This study was aimed to formulate and evaluate an orally disintegrating tablet (ODT containing ondansetron while using semi-synthetic and natural superdisintegrants. Methods: Orodispersible tablets were prepared by direct compression using natural superdisintegrant (Karaya gum and semi-synthetic superdisintegrant (croscarmellose. The prepared tablets were evaluated for hardness, friability, thickness, drug content uniformity, water absorption and wetting time. A 32 factorial design was used to investigate the effect of independent variables (amount of croscarmellose and Karaya gum on dependent variables (disintegration time, friability and Q5 [cumulative amount of drug release after 5 minutes]. A counter plot was also presented to graphically represent the effect of independent variable on the disintegration time, friability and Q5. The check point batch was also prepared to prove the validity of the evolved mathematical model. The systematic formulation approach helped in understanding the effect of formulation processing variable. Results: According to the results of optimized batches, the best concentrations of superdisintegrant were as follows: 7.88 mg Karaya gum and 7.78 mg croscarmellose gave rapid disintegration in 31 seconds which showed 99% drug release within 5 minutes. Conclusion: Karaya gum, a natural superdisintegrant, gives a rapid disintegration and high release when used with synthetic superdisintegrant in formulation of ODT.
Full Text Available Desmoperssin is the drug of choice for treatment of central diabetes insipidus and most commonly it is used as intranasal spray. In this study, efficacy and side effects of oral desmopressin was compared with the intranasal spray. This study was before -after clinical trial on 14 outpatients (9 F, 5 M, age 14 -50 Y with central diabetes insipidus who had been treated with intranasal spray of desmopressin previously. Weight, pulse rate and blood pressure (sitting -standing, biochemical profile, serum electrolytes, 24h urine volume, specific gravity of urine and LFT was measured before and after 1 month study. Starting dose for each patient was one oral tablet of DDAVP (0.1 mg per 8 hours. Paired Samples T-Test was used for data analysis. No clinically significant changes were found as regard to weight, pulse rate, blood pressure, blood chemistry, electrolyte and urinalysis. Single reported adverse effect was headache (43% in tablet group and dyspnea (7% in spray group. Both dosage forms were able to control diurnal polyuria and nocturnal polyuria. The antidiuretic dose - equivalence ratio for intranasal to oral desmopressin was 1: 18. Spray was superior in terms of rapid onset of action and duration of antidiuretic action in 100% and 78% of cases (not significant, respectively. Tablets were more available and much more easily consumed as reported by patients, in 86% (P=0.0006. Treatment with tablets offers a good alternative to the intranasal route, especially in patients with chronic rhinitis or common cold and similar conditions.
Arın Gül Dal
piroxicam in tablets. The separation of piroxicam was conducted in a fused-silica capillary by using 10 mM borate buffer (pH 9.0 containing 10% (v/v methanol as background electrolyte. The optimum conditions determined were 25 kV for separation voltage and 1 s for injection time. Analysis was carried out with UV detection at 204 nm. Naproxen sodium was used as an internal standard. The method was linear over the range of 0.23–28.79 µg/mL. The accuracy and precision were found to be satisfied within the acceptable limits (<2%. The LOD and LOQ were found to be 0.07 and 0.19 µg/mL, respectively. The method described here was applied to tablet dosage forms and the content of a tablet was found in the limits of USP-24 suggestions. To compare the results of capillary electrophoretic method, UV spectrophotometric method was developed and the difference between two methods was found to be insignificant. The capillary zone electrophoretic method developed in this study is rapid, simple, and suitable for routine analysis of piroxicam in pharmaceutical tablets.
Full Text Available Objective: To formulate and Characterize Mouth Dissolving Tablet of Zolmitriptan to produce the intended benefits. Methods: Tablets were prepared using a direct compression method employing superdisintegrants such as Kyron T-314, Crospovidone, Croscarmellose Sodium, and Sodium Starch Glycolate. Tablets of Zolmitriptan prepared using Kyron T-314 exhibited the least friability and disintegration time 35 seconds. To decrease the disintegration time further, a sublimation technique was used along with the superdisintegrants for the preparation of Mouth Dissolving Tablet (MDTs. The addition of camphor as a subliming agent lowered the disintegration time 10 seconds further, but the percent friability was increased. A 32 full factorial design was employed to study the joint influence of the amount of superdisintegrant (Kyron T-314 and the amount of sublimating agent (Camphor on the percent of friability and the disintegration time. Results: The results of multiple linear regression analysis revealed that an effective MDT of Zolmitriptan requires higher percentages of Kyron T-314 and camphor should be used. The approach using the optimization technique helped to produce a detailed understanding effect of formulation parameters. An optimized formulation was found to have good hardness, wetting time, disintegration time. Release kinetic model study indicated that all the formulations follow zero order kinetics. It also indicated that batch F1, F2, F5 and F8 releases the drug at constant rate as well as fast rate as per the Weibull model which was also confirmed by HixsonCrowell model. Stability studies indicated that there are no significant changes in hardness, Percentage friability, drug content and in-vitro disintegration time and cumulative percentage drug release. Conclusions: Thus, it was concluded that by adopting a systematic formulation approach, Zolmitriptan Mouth dissolving tablet could be formulated using superdisintegrants in combination with
Wegehaupt, Florian J; Lunghi, Nancy; Hogger, Vanessa M G; Attin, Thomas
The extrinsic sources for erosion-causing acids are primarily acidic beverages and foodstuffs. Effervescent tablets also contain organic acids (e.g. citric, tartaric, malic) in order to form carbon dioxide by contact with water with the help of the carbonate salts of the tablets. To adequately inform patients about the possible erosive potential of effervescent tablets, this study was undertaken in order to investigate the erosive potential of effervescent tablets (ET), containing either a combination of vitamins and minerals or vitamins only, commercially available in Switzerland. One hundred and ninety-two bovine enamel samples were prepared and allocated to 16 groups (AH and 18; n = 12/group). Samples were eroded (120 s/erosive cycle) in freshly prepared solutions (200 ml/12 samples) comprised of tap water and a supplement as follows: none (control groups, A and 1); vitamin+mineral ET: Qualite and Prix (B), Optisana (C), Well and Active (D), Actilife All in One (E), Berocca (F), Isostar (G) and Qualite and Prix Mg + Vit C (H); vitamin ET: Actilife-Multivitamin (2), Sunlife Vitamin C (3), Optisana Vitamin C (4), Optisana Multivitamin (5), Well and Active Multivitamin (6), Kneipp Vitamin C+Zink (7) and Sunlife Multivitamin (8). Enamel loss was measured using profilometry after 10 and 20 erosive cycles. For the vitamin+mineral ET, no loss was observed in groups BE. Significantly highest enamel loss (mean ± SD) after 20 cycles was observed for Isostar (5.26 ± 0.76 µm) and Qualite and Prix Mg + Vit C (5.12 ± 0.67 µm). All vitamine ET showed erosive enamel loss. Significantly highest loss was observed for Sunlife Multivitamin (8.45 ± 1.08 µm), while the lowest loss was observed for Actilife-Multivitamin (5.61 ± 1.08 µm) after 20 cycles. Some of the tested effervescent tablets showed a considerable erosive potential and patients should be informed accordingly.
Veitia, Reiner A; Potier, Marie Claude
Single-gene deletions, duplications, and misregulation, as well as aneuploidy, can lead to stoichiometric imbalances within macromolecular complexes and cellular networks, causing their malfunction. Such alterations can be responsible for inherited or somatic genetic disorders including Mendelian diseases, aneuploid syndromes, and cancer. We review the effects of gene dosage alterations at the transcriptomic and proteomic levels, and the various responses of the cell to counteract their effects. Furthermore, we explore several biochemical models and ideas that can provide the rationale for treatments modulating the effects of gene dosage imbalances. Copyright © 2015 Elsevier Ltd. All rights reserved.
Ruiz-Caro, Roberto; Gago-Guillan, Manuel; Otero-Espinar, Francisco Javier; Veiga, María Dolores
Mucoadhesive chitosan (CS) and/or hydroxypropyl-methylcellulose (HPMC) tablets for gastric drug delivery of acyclovir (ACV) have been developed in order to improve the ACV oral bioavailability. Swelling, bioadhesive and dissolution studies were carried out in two acidic media (pH 1.5 and 4) in order to determine the tablets behaviour in both fed and fasted states. All the designed tablets showed good mucoadhesive properties on gastric mucosa due to the presence of CS and/or HPMC. In vitro dissolution of ACV from tablets was influenced by the swelling behaviour of each polymer. All data release of the studied tablets fitted to Hopfenberg model, which describes drug release from tablets displaying heterogeneous erosion. HPMC and CS/HPMC tablets revealed a sustained release for 24 h, but a complete dissolution of the tablets was not produced at this time. On the contrary, tablets which contained only CS as polymer were able to release the total amount of ACV for 4 h, due to the CS imbibition and erosion processes in pH 1.5 medium. These results allowed us to conclude that CS is the excipient to be chosen to obtain gastroretentive formulations, due to its demonstrated gastric compatibility.
Seitavuopio, Paulus; Rantanen, Jukka; Yliruusi, Jouko
The aim of this study was to characterise tablet surfaces using different imaging and roughness analytical techniques including optical microscopy, scanning electron microscopy (SEM), laser profilometry and atomic force microscopy (AFM). The test materials compressed were potassium chloride (KCl......) and sodium chloride (NaCl). It was found that all methods used suggested that the KCl tablets were smoother than the NaCl tablets and higher compression pressure made the tablets smoother. Imaging methods like optical microscopy and SEM can give useful information about the roughness of the sample surface...
Shah, Ritesh; Patel, Sachin; Patel, Hetal; Pandey, Sonia; Shah, Shailesh; Shah, Dinesh
The aim of present research was to produce carvedilol compression coated tablet to provide biphasic drug release. A compressed coated tablet made of a sustained release core tablet and an immediate release coat tablet. Both the core and the coat contained carvedilol. The sustained release effect was achieved with polymers (HPMC K4M and PEO WSR 205) to modulate the release of the drug. The powder blends for core and coat tablets were evaluated for angle of repose, bulk density, compressibility index, and drug content. Compressed coated tablets were evaluated for thickness, diameter, weight variation test, drug content, hardness, friability, disintegration and in vitro release studies. The powder blends showed satisfactory flow properties, compressibility, drug content and all the tablet formulations showed acceptable pharmaco-technical properties. Carvedilol contained in the fast releasing component was released within 3 min, whereas the drug in the core tablet was released at different times up to 24 h, depending on the composition of the matrix tablet. The mechanism of drug release was fickian diffusion or anomalous behavior. Batch F7, containing 10 mg PEO WSR 205 and 5 mg HPMC K4M, showed maximum similarity with theoretical profile and zero order drug release kinetic.
Full Text Available The gastroretentive dosage form is designed to prolong the gastric residence time of the drug delivery system whichalso results in the development of an appropriate excipient. The purpose of this study is to develop and characterize coprocessedexcipient made from carrageenan (kappa-iota = 1:1 and pregelatinized cassava starch propionate (PCSP inratios of 1:1, 1:2, and 1:3. PCSP was prepared with propionic anhydride in an aqueous medium. The product was mixedwith carrageenan (kappa-iota = 1:1, as well as characterized physicochemical and functional properties. The coprocessedexcipient was then used as a mucoadhesive granule and floating tablet. The USP Basket was selected toperform the dissolution test of the granules in HCl buffer (pH 1.2 and distilled water for 8 hours each. Mucoadhesiveproperties were evaluated using bioadhesive through a vitro test and wash-off test. As for the floating tablet, the USPPaddle was selected to perform the dissolution test of the tablets in 0.1 N HCl for 10 hours. The floating lag time andfloating time were tested in 0.1 N HCl for 24 hours. The result of these studies indicated that co-processed excipientcarrageenan-PCSP can retard dosage form in gastric and drug controlled release, thus making it a suitable material forthe gastroretentive dosage form.
. Resulting granules were compressed to 500 mg tablets using a single punch machine. The tablets were subjected to hardness, friability, disintegration and dissolution tests. RESULTS: The granules formed hard tablets (tensile strength 1 - 2.0 ...
David W. Pittman
Full Text Available Negative hedonic sensory qualities of HIV antiretroviral drugs often reduce patient adherence particularly in pediatric populations requiring oral consumption. This study examines the palatability of an innovative delivery mechanism utilizing a freeze-drying-in-blister approach to create fast-dissolving tablets (FDTs containing a fixed-dose combination of lopinavir and ritonavir (LPV/r. Consumption patterns of solutions during brief-access and long-term testing and baby foodstuff consumption were analyzed to evaluate the orosensory detection and avoidance of placebo FDTs containing no LPV/r (FDT− and FDTs containing LPV/r (FDT+. Rats showed no change in consumption patterns for the placebo FDT− compared with control solutions. Rats can detect but do not avoid FDT+ at body-weight-adjusted dosages in both brief-access (30-s and long-term (23 h consumption tests. There is an aversive response to concentrated doses of FDT+ during brief-access tests that cannot be masked by 25% sucrose. However, the strongest FDT+ concentration was not rejected when mixed with 50 g of applesauce, banana sauce, or rice cereal baby foodstuffs. The averseness of the FDT+ was associated with the presence of LPV/r and not the FDT− formulation itself. The novel FDT formulation appears to be a palatable delivery mechanism for oral antiretroviral pharmaceuticals especially when mixed with baby foodstuffs.
Just, Sarah; Toschkoff, Gregor; Funke, Adrian; Djuric, Dejan; Scharrer, Georg; Khinast, Johannes; Knop, Klaus; Kleinebudde, Peter
The objective of this study was to enhance the inter-tablet coating uniformity in an active coating process at lab and pilot scale by statistical design of experiments. The API candesartan cilexetil was applied onto gastrointestinal therapeutic systems containing the API nifedipine to obtain fixed dose combinations of these two drugs with different release profiles. At lab scale, the parameters pan load, pan speed, spray rate and number of spray nozzles were examined. At pilot scale, the parameters pan load, pan speed, spray rate, spray time, and spray pressure were investigated. A low spray rate and a high pan speed improved the coating uniformity at both scales. The number of spray nozzles was identified as the most influential variable at lab scale. With four spray nozzles, the highest CV value was equal to 6.4%, compared to 13.4% obtained with two spray nozzles. The lowest CV of 4.5% obtained with two spray nozzles was further reduced to 2.3% when using four spray nozzles. At pilot scale, CV values between 2.7% and 11.1% were achieved. Since the test of uniformity of dosage units accepts CV values of up to 6.25%, this active coating process is well suited to comply with the pharmacopoeial requirements. Copyright © 2013 Elsevier B.V. All rights reserved.
Wenzel, Tim; Stillhart, Cordula; Kleinebudde, Peter; Szepes, Anikó
Drug load plays an important role in the development of solid dosage forms, since it can significantly influence both processability and final product properties. The percolation threshold of the active pharmaceutical ingredient (API) corresponds to a critical concentration, above which an abrupt change in drug product characteristics can occur. The objective of this study was to identify the percolation threshold of a poorly water-soluble drug with regard to the dissolution behavior from immediate release tablets. The influence of the API particle size on the percolation threshold was also studied. Formulations with increasing drug loads were manufactured via roll compaction using constant process parameters and subsequent tableting. Drug dissolution was investigated in biorelevant medium. The percolation threshold was estimated via a model dependent and a model independent method based on the dissolution data. The intragranular concentration of mefenamic acid had a significant effect on granules and tablet characteristics, such as particle size distribution, compactibility and tablet disintegration. Increasing the intragranular drug concentration of the tablets resulted in lower dissolution rates. A percolation threshold of approximately 20% v/v could be determined for both particle sizes of the API above which an abrupt decrease of the dissolution rate occurred. However, the increasing drug load had a more pronounced effect on dissolution rate of tablets containing the micronized API, which can be attributed to the high agglomeration tendency of micronized substances during manufacturing steps, such as roll compaction and tableting. Both methods that were applied for the estimation of percolation threshold provided comparable values.
Hamman, Hannlie; Hamman, Josias; Wessels, Anita; Scholtz, Jacques; Steenekamp, Jan
The SeDeM Expert Diagram System (SeDeM EDS) was originally developed to provide information about the suitability of powders to produce direct compressible tablets. Multiple-unit pellet systems (MUPS) are dosage forms consisting of pellets compressed into tablets or loaded into hard gelatine capsules. The aim of this study was to apply the SeDeM EDS to different size pellets (i.e. 0.5, 1.0, 1.5, 2.0 and 2.5 mm) containing different APIs (i.e. doxylamine, ibuprofen or paracetamol) to determine which properties should be corrected to yield MUPS tablet formulations. The SeDeM parameter tests were conducted on the pellets, selected excipients, intermediate blends and final blends. The study showed that the properties of the pellets depended on the active ingredient and pellet size. The SeDeM compressibility indices indicated that the final pellet blends should be suitable for compression into MUPS tablets. MUPS tablets were prepared from the final blends and evaluated in terms of physico-chemical properties and dissolution profiles. Only three of the MUPS tablet formulations containing ibuprofen and one MUPS tablet formulation containing paracetamol failed content uniformity. The water solubility of the APIs as well as the pellet size (surface area exposed to the dissolution medium) attributed to the difference in drug dissolution rate.
Li, Lian; Zang, Hengchang; Li, Jun; Chen, Dejun; Li, Tao; Wang, Fengshan
Vibrational spectroscopy including Raman and near-infrared (NIR) spectroscopy has become an attractive tool for pharmaceutical analysis. In this study, effective calibration models for the identification of anisodamine tablet and its counterfeit and the distinguishment of manufacturing plants, based on Raman and NIR spectroscopy, were built, respectively. Anisodamine counterfeit tablets were identified by Raman spectroscopy with correlation coefficient method, and the results showed that the predictive accuracy was 100%. The genuine anisodamine tablets from 5 different manufacturing plants were distinguished by NIR spectroscopy using partial least squares discriminant analysis (PLS-DA) models based on interval principal component analysis (iPCA) method. And the results showed the recognition rate and rejection rate were 100% respectively. In conclusion, Raman spectroscopy and NIR spectroscopy combined with chemometrics are feasible and potential tools for rapid pharmaceutical tablet discrimination. Copyright © 2014 Elsevier B.V. All rights reserved.
Novikova, Anna; Carstensen, Jens Michael; Rades, Thomas
In the present study the applicability of multispectral UV imaging in combination with multivariate image analysis for surface evaluation of MUPS tablets was investigated with respect to the differentiation of the API pellets from the excipients matrix, estimation of the drug content as well...... as pellet distribution, and influence of the coating material and tablet thickness on the predictive model. Different formulations consisting of coated drug pellets with two coating polymers (Aquacoat(®) ECD and Eudragit(®) NE 30 D) at three coating levels each were compressed to MUPS tablets with various...... amounts of coated pellets and different tablet thicknesses. The coated drug pellets were clearly distinguishable from the excipients matrix using a partial least squares approach regardless of the coating layer thickness and coating material used. Furthermore, the number of the detected drug pellets...
Tayebi, Hoda; Mortazavi, Seyed Alireza
Orally disintegrating tablets (ODTs) are capable of turning quickly into a liquid dosage form in contact with the saliva, thus possessing the advantages of both the solid dosage forms particularly stability and liquid dosage forms specially ease of swallowing and pre-gastric absorption of drug. The aim of this study was to prepare a novel matrix-type buccal fast disintegrating ibuprofen tablet formulation using special polymers, water soluble excipients, super-disintegrants and quickly soluble granules. For this purpose different tablet formulations of ibuprofen were prepared. The amount of ibuprofen in each formulation was 100 mg. Eight groups of formulation were prepared (A-H series), accounting for a total number of 45 formulations. Formulations prepared were examined in terms of different physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Results of formulation F22a (in series F), was found to be acceptable, making it the chosen formulation for further studies. Then, by adding various flavorants and sweeteners to this formulation, complementary series of formulations, named G and H, were prepared. Following the comparison of their taste with each other through asking 10 volunteers, the most suitable formulation regarding the taste, being formulation F22s, was chosen as the ultimate formulation. This formulation had PVP, ibuprofen and croscarmellose as the intra-granular components and xylitol and saccharin as the extra-granular ingredients. Formulation F22s was found to be acceptable in terms of physicochemical tests conducted, showing quick disintegration within the buccal cavity, appropriate hardness and rather low friability. Hence formulation F22s was selected as the final formulation.
Klukkert, Marten; Wu, Jian Xiong; Rantanen, Jukka
Quality control of tablets and its primary packing material within the manufacturing line requires analytical routines that allow monitoring of the desired product attributes with high efficiency. The aim of this study was to evaluate the suitability of multispectral UV imaging combined with mult......Quality control of tablets and its primary packing material within the manufacturing line requires analytical routines that allow monitoring of the desired product attributes with high efficiency. The aim of this study was to evaluate the suitability of multispectral UV imaging combined...... with multivariate image analysis for verification of blister pack filling, differentiation of tablets of varying composition therein, as well as detection of imprint defects and surface cracks of bulk tablets. Moreover, the influence of polymer sealing foils on tablet characterization within blister cavities...... was investigated. Several tablets of different composition were imaged either as bulk, within unsealed blister packs, or within blister packs that were manually sealed with three different types of either PVC or PCTFE foils. It was demonstrated that UV imaging is a fast and reliable technique for counting...
Conclusion: Cefixime trihydrate can be effectively formulated as an oral controlled release mucoadhesive tablet using RSM, and it is possible to achieve adequate mucoadhesive strength and the desired release profile with the optimum combination of polymers.
in the female, or in Muller's terms, depression of X-linked activity in the female. The rapid acceptance of X inactivation as the underlying mechanism of mammalian dosage com- pensation was probably due to the accompanying easily visi- ble Barr body or heteropycnotic X chromosome, an accepted marker of genetic ...
Landová, Hana; Daněk, Zdeněk; Gajdziok, Jan; Vetchý, David; Stembírek, Jan
Mucoadhesion is a specific phenomenon of creating bonds during intimate contact between biological surfaces covered by a mucus layer and a mucoadhesive material. In recent years come to the forefront of interest in the pharmaceutical industry modern dosage forms based on this specific process. Films (discs, patches) composed of mucoadhesive polymers (cellulose derivatives, polyacrylates, polyoxyethylene, etc.) prepared by established methods (solvent casting, hot melt extrusion, etc.) could be perspective candidates for oral administration of many drugs due to their flexibility and comfortable use. In addition, they can circumvent the relatively short residence time of conventional oral dosage forms on the mucosa and provide a precisely measured drug dose to the application site. Moreover, they can also help to protect the wound surface, thus help to reduce pain and improve effectiveness of the therapy. The aim of this article is to give an overview about the principles of creation of mucoadhesive bonds and about novel dosage form - mucoadhesive films in terms of their composition, preparation and practical usage. oral mucosa mucoadhesion principles mucoadhesive dosage forms films patches discs.
Hughey, Justin R; Keen, Justin M; Miller, Dave A; Kolter, Karl; Langley, Nigel; McGinity, James W
The dissolution enhancement advantages inherent to amorphous solid dispersions systems are often not fully realized once they are formulated into a solid dosage form. The objective of this study was to investigate the ability of inorganic salts to improve the dissolution rate of carbamazepine (CBZ) from tablets containing a high loading of a Soluplus®-based solid dispersion. Cloud point and viscometric studies were conducted on Soluplus® solutions to understand the effect of temperature, salt type and salt concentration on the aqueous solubility and gelling tendencies of Soluplus®, properties that can significantly impact dissolution performance. Studies indicated that Soluplus® exhibited a cloud point that was strongly dependent on the salt type and salt concentration present in the dissolving medium. The presence of kosmotropic salts dehydrated the polymer, effectively lowering the cloud point and facilitating formation of a thermoreversible hydrogel. The ability of ions to impact the cloud point and gel strength generally followed the rank order of the Hofmeister series. Solid dispersions of CBZ and Soluplus® were prepared by KinetiSol® Dispersing, characterized to confirm an amorphous composition was formed and incorporated into tablets at very high levels (70% w/w). Dissolution studies demonstrated the utility of including salts in tablets to improve dissolution properties. Tablets that did not contain a salt or those that included a chaotropic salt hydrated at the tablet surface and did not allow for sufficient moisture ingress into the tablet. Conversely, the inclusion of kosmotropic salts allowed for rapid hydration of the entire tablet and the formation of a gel structure with strength dependent on the type of salt utilized. Studies also showed that, in addition to allowing tablet hydration, potassium bicarbonate and potassium carbonate provided effervescence which effectively destroyed the gel network and allowed for rapid dissolution of CBZ
Poornima R. Shetty
Full Text Available Two simple, accurate, precise, economical procedures, entailing neither irksome sample treatment nor tedious extraction process have been developed for the simultaneous estimation of rabeprazole sodium and levosulpiride in combined tablet dosage form. The first method was based on employing simultaneous equation method for analysis of both drugs. Rabeprazole sodium and levosulpiride have shown absorbance maxima at 284 and 232 nm in methanol, respectively. The second method was based on derivative spectrophotometric method involving the determination of both the drugs at their respective zero crossing point (ZCP. The first order derivative spectrum was obtained in methanol and the determinations were made at 231.2 nm (ZCP of levosulpiride for rabeprazole sodium and 246.2 nm (ZCP of rabeprazole sodium for levosulpiride. The linearity was obeyed in the concentration range of 1-20 μg/ml for both drugs. The medium of dissolution was used 900 ml of phosphate buffer pH 7.4 using a USP type 2 apparatus at a stirring rate of 100 rpm. The drug release was evaluated by developed spectroscopic methods. The suitability of the developed method for quantitative determination of rabeprazole sodium and levosulpiride was proved by validation.
Full Text Available A simple, precise, accurate, and economical spectrophotometric method has been developed for simultaneous estimation of levocetirizine dihydrochloride (LCT and phenylephrine hydrochloride (PHE by employing first-order derivative spectrophotometric method. The first-order derivative absorption at 240 nm (zero crossing point of PHE was used for quantification of LCT and 283.2 nm (zero crossing point of LCT for quantification of PHE. The linearity was established over the concentration range of 4–24 μg/mL and 8–48 μg/mL for LCT and PHE with correlation coefficients (r2 0.9964 and 0.9972, respectively. The mean % recoveries were found to be in the range of 99.14%–100.43% for LCT and 98.73%–100.83% for PHE. The proposed method has been validated as per ICH guideline and successfully applied for the simultaneous estimation of LCT and PHE in combined tablet dosage form.
Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang
® film to produce pulsatile tablet of amoxicillin. In vitro release study firstly indicated a three-pulse release profile of the tablet. Later the pulse tablet was found to generate the sustained release of amoxicillin in beagle dogs. Furthermore, the Simcyp® software was used to simulate the in vivo concentration time curve model of the three-pulse release tablet for amoxicillin in both human and beagle dog. The prediction by PBPK model nicely fitted the observation in human and beagle dog. Conclusions This study has demonstrated the interrelation of factors affecting the pulsatile formulation of amoxicillin using a Box–Behnken design. The three-pulse release tablets of amoxicillin were proven to generate pulsatile release in vitro and sustained release in vivo. This formulation was also found to extend the effective plasma concentration in human compared to the tablet of immediate release based on the simulation data by PBPK modeling. This study provides an example of using PBPK to guide the development of pulsatile dosage forms. PMID:27479702
Li, Jin; Chai, Hongyu; Li, Yang; Chai, Xuyu; Zhao, Yan; Zhao, Yunfan; Tao, Tao; Xiang, Xiaoqiang
amoxicillin. In vitro release study firstly indicated a three-pulse release profile of the tablet. Later the pulse tablet was found to generate the sustained release of amoxicillin in beagle dogs. Furthermore, the Simcyp® software was used to simulate the in vivo concentration time curve model of the three-pulse release tablet for amoxicillin in both human and beagle dog. The prediction by PBPK model nicely fitted the observation in human and beagle dog. This study has demonstrated the interrelation of factors affecting the pulsatile formulation of amoxicillin using a Box-Behnken design. The three-pulse release tablets of amoxicillin were proven to generate pulsatile release in vitro and sustained release in vivo. This formulation was also found to extend the effective plasma concentration in human compared to the tablet of immediate release based on the simulation data by PBPK modeling. This study provides an example of using PBPK to guide the development of pulsatile dosage forms.
Jeske, Daniel R.
BACKGROUND: Tumescent lidocaine anesthesia consists of subcutaneous injection of relatively large volumes (up to 4 L or more) of dilute lidocaine (≤1 g/L) and epinephrine (≤1 mg/L). Although tumescent lidocaine anesthesia is used for an increasing variety of surgical procedures, the maximum safe dosage is unknown. Our primary aim in this study was to measure serum lidocaine concentrations after subcutaneous administration of tumescent lidocaine with and without liposuction. Our hypotheses were that even with large doses (i.e., >30 mg/kg), serum lidocaine concentrations would be below levels associated with mild toxicity and that the concentration-time profile would be lower after liposuction than without liposuction. METHODS: Volunteers participated in 1 to 2 infiltration studies without liposuction and then one study with tumescent liposuction totally by local anesthesia. Serum lidocaine concentrations were measured at 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 24 hours after each tumescent lidocaine infiltration. Area under the curve (AUC∞) of the serum lidocaine concentration-time profiles and peak serum lidocaine concentrations (Cmax) were determined with and without liposuction. For any given milligram per kilogram dosage, the probability that Cmax >6 μg/mL, the threshold for mild lidocaine toxicity was estimated using tolerance interval analysis. RESULTS: In 41 tumescent infiltration procedures among 14 volunteer subjects, tumescent lidocaine dosages ranged from 19.2 to 52 mg/kg. Measured serum lidocaine concentrations were all lidocaine toxicity without liposuction at a dose of 28 mg/kg and with liposuction at a dose of 45 mg/kg was ≤1 per 2000. CONCLUSIONS: Preliminary estimates for maximum safe dosages of tumescent lidocaine are 28 mg/kg without liposuction and 45 mg/kg with liposuction. As a result of delayed systemic absorption, these dosages yield serum lidocaine concentrations below levels associated with mild toxicity and are a nonsignificant
Full Text Available The aim of this study was to find the optimal tablet composition with maximum content of dried fruits (Cornus mas L.. The effect of three different concentrations (12.5, 25 and 50 % of two types of microcrystalline cellulose (Avicel® PH 101 and Avicel® PH 200 and three different compression pressures (20, 60 and 100 MPa on the physical properties of tablet blends and tablets was studied. Tablets containing 50 % Avicel® PH 101 compressed under 100 MPa were found to have the best physical properties. This combination of composition and compression pressure resulted in stable tablets even after storage under accelerated stability conditions (6 months, 40 °C and 75 % RH.
Full Text Available The development of pumpkin tablet was studied and the drying conditions of pumpkin using a double drum dryer were optimized. The study factors were drying agents (maltodextrin D.E.13-16 andtapioca flour at different levels (3 and 5%, drying temperatures (130 and 140oC and drum dryer speeds (4 and 5 rpm. The results showed that the optimal conditions were using 3% maltodextrin D.E.13-16, dryingtemperature of 130oC and drum dryer speed of 4 rpm. The moisture, fat, bulk density, reducing sugars and granulometric retention of the obtained pumpkin powder were 3.39%, 1.42%, 1.004 g/ml, 12.63% and 0.67%, respectively and L*, a* and b* values were 73.85, -0.60 and 35.23, respectively. A study of suitable amount of icing sugar using different contents for tablet production (0, 10, 20, 30 and 40% was performedand showed that using 20% icing sugar was the most acceptable. The obtained pumpkin tablet was subjected to chemical, physical and microbiological analysis. The ash, moisture, protein, fat, fiber and carbohydratecontents were 1.87, 3.60, 3.34, 1.00, 2.26 and 87.99%, respectively. The reducing sugars and β-carotene contents were 5.44±0.61% and 3.79±0.57 mg/100g, respectively. The Aw, hardness and solubility were 0.56,3.25 kgf and 25.00 %, respectively. The L*, a* and b* values were 79.85, 0.28 and 23.64, respectively. The total microbial count and the yeast and mould count were <10 CFU/g. The shelf life of the pumpkin tabletwas at least 4 months at room temperature (35±2oC.
Kaneko, Sunao; Inoue, Yushi; Sasagawa, Mutsuo; Kato, Masaaki
To compare the tolerability and efficacy of two titration methods (rapid and slow titration) for TOPINA Tablets with different dosages and periods of escalation, a double-blind comparative study was conducted in patients with localization-related epilepsy. A total of 183 patients were randomized to either rapid titration (initial dosage 100 mg/day increased by 100-200 mg at weekly intervals) or to slow titration (initial dosage 50 mg/day increased in 50 mg/day increments at weekly intervals). TOPINA Tablets were administered for 12 weeks to the maximum dosage of 400 mg/day. The incident of adverse events leading to treatment interruptions or withdrawals was 18.9% in rapid titration and 14.8% in slow titration, with no statistical significance (p = 0.554). The incident of adverse events and adverse reactions of slow titration was slightly lower than that of rapid titration. The common adverse events and adverse reactions reported in the two titration methods were comparable and were well tolerated. On the other hand, the efficacy of slow titration, percent reduction in seizure rate and responder rate, was comparable with that of rapid titration. In conclusion, there were no significant differences of therapeutic response to TOPINA Tablets between the two titration methods.
Johnson, Elizabeth J; Vishwanathan, Rohini; Rasmussen, Helen M; Lang, John C
The benefits of antioxidant micronutrients in slowing progression to advanced stages of age-related macular degeneration (AMD) was supported by the 4/day tablet form investigated in the Age-related Eye Disease Study 1 (AREDS1) and the 2/day softgel form in the Age-related Eye Disease Study 2 (AREDS2). However, the choices of excipient, dosage form, and ingredient chemistry as well as the patient physiologies and pathologies can influence bioavailability and efficacy. The objective of the study was to explore the influence of dosage form on the bioavailability of the five primary AREDS1 and Tier-2 AREDS2 micronutrients: the metals zinc and copper, β-carotene, and vitamins E and C. The intent was to establish by chemical analysis the relative bioavailabilities of these five micronutrients in plasma, or serum for the metals, as well as to identify any opportunities for improvements. A total of 15 healthy men (5) and women (10) were recruited for a controlled, randomized, three-arm, crossover trial of the AREDS1 micronutrients. The study investigated responses in bioabsorption to a single dose of either four tablets or two softgels at the full dose level, or one softgel at the half-dose level. The bioavailability of each micronutrient was based on the pharmacokinetic profiles established through 15 samplings for each ingredient/dosage form in plasma/serum over the course of one week. Bioavailability was estimated using model-independent and model-dependent procedures. A statistical advantage of the dosage form was observed in only two cases from the exaggerated effects using the half-dose softgel and for the tablet dosage form for β-carotene and vitamin E. An unanticipated complexity was suggested by the bimodal absorption of zinc. For these micronutrients, no disadvantage (though potential advantage) was inferred for the water-soluble components presented in a softgel formulation. Increased fractional absorption was observed for the smaller dose (one capsule versus
Eurell, Jo Ann C; Diamond, Nancy A; Buie, Brandon; Grant, David; Pijanowski, Gerald J
Tablet computers offer a new method of information management in veterinary medical education. With the tablet computer, students can annotate class notes using electronic ink, search for keywords, and convert handwriting to text as needed. Additional electronic learning resources, such as medical dictionaries and electronic textbooks, can be readily available. Eleven first-year veterinary students purchased tablet computers and participated in an investigation of their working methods and perceptions of the tablet computer as an educational tool. Most students found the technology useful. The small size and portability of the tablet allowed easy transport and use in a variety of environments. Most students adapted to electronic notetaking by the second week of classes; negative experiences with the tablet centered on a failure to become comfortable with taking notes and navigating on the computer as opposed to writing and searching on paper. A few performance-related problems, including short battery life, were reported. Tablet software allowed conversion of faculty course notes from a variety of original formats, meaning that instructors could maintain their original methods of note preparation. Adopting a consistent naming convention for files helped students to locate the files on their computers, and smaller file sizes helped with computer performance. Collaboration between students was fostered by tablet use, which offers possibilities for future development of collaborative learning environments.
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Nitenpyram tablets. 520.1510 Section 520.1510 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... order of a licensed veterinarian. (d) Conditions of use—(1) Dogs—(i) Amount—(A) One 11.4-mg tablet for...
... for use of 50 and 250 milligram tablets. (c) Conditions of use in dogs—(1) Amount. Twenty-five... information. (2) Indications for use. For the control of convulsions associated with idiopathic epilepsy... recognizable lesion in certain entities in dogs.1 (3) Limitations. The tablets may be administered whole or...
Purpose: To develop and validate a suitable method for the assay of metformin hydrochloride (HCl) in tablets containing croscarmellose sodium as an additive. Methods: Methanol and ethanol (99%) were assessed as solvents for sample preparation for the assay of metformin HCl in tablets containing croscarmellose ...
E – contains a pattern that can well be interpreted as another calendrical instruction, quite similar in nature to the Mamari calendar. Engraved on tablet Keiti is a string of glyphs known as sequence alpha 1-10, which is repeated 10 times throughout one side of the tablet. This repetitious string...
Purpose: To investigate the pharmacokinetics of of a developed metoprolol and a reference standard (Mepressor®). Methods: Metoprolol tartrate-loaded Eudragit® FS microparticles were formulated and compressed into tablets. The tablets were tested for their physicochemical properties according to United States ...
Sargent, Lana; Miles, Elizabeth
Identifying the most effective models for integrating new technology into the classroom and understanding its effects on educational outcomes are essential for nurse educators. This article describes an educational intervention with tablet technology (iPads) using an innovative case-based learning model in a nursing program. Students reported positive learning outcomes when using the tablet technology for learning course content.
van Santen, E; Barends, D M; Frijlink, H W
The literature was reviewed regarding advantages, problems and performance indicators of score lines. Scored tablets provide dose flexibility, ease of swallowing and may reduce the costs of medication. However, many patients are confronted with scored tablets that are broken unequally and with
Purpose: The purpose of the present research was to the effect of camphor as a subliming agent on the mouth dissolving property of famotidine tablets. Method: Orodispersible tablets of famotidine were prepared using camphor as subliming agent and sodium starch glycollate together with crosscarmellose sodium as ...
Rygnestad, T; Zahlsen, K; Samdal, F A
The aim of this study was to compare the rate of absorption between ordinary paracetamol tablets and effervescent paracetamol tablets. Twenty healthy volunteers participated in an open randomised crossover study and were given a 1000-mg dose of either ordinary paracetamol tablets (2 x 500 mg Panodil tablets, SmithKline Beecham) or effervescent paracetamol tablets (2 x 500 mg Pinex Brusetablett, Alpharma AS) with a 3-week washout period in between. Blood samples were collected for 3 h. Maximum serum concentration (Cmax) and the time to maximum serum concentration (tmax) were recorded and the area under the concentration versus time curve (AUC) was calculated. The mean tmax was significantly shorter when paracetamol effervescent tablets were taken (27 min) rather than ordinary paracetamol tablets (45 min) (P = 0.004). There was no significant difference between the mean Cmax of 143 micromol/l with effervescent tablets and that of 131 micromol/l with ordinary tablets. The mean AUC(0-3 h) was significantly higher with paracetamol effervescent tablets (223.8 micromol x h x l(-1)) than with ordinary tablets (198.2 micromol x h x l(-1); P = 0.003). After 15 min, 17 (85%) subjects in the effervescent group had a serum concentration of 70 micromol/l (lower therapeutic serum concentration) or higher relative to only 2 (10%) subjects in the ordinary tablet group (P = 0.001). Paracetamol effervescent tablets are absorbed significantly faster than ordinary paracetamol. Thus, effervescent tablets might offer significantly faster pain relief when paracetamol is used.
Koga, Arthur T; Strauss, John; Zai, Clement; Remington, Gary; De Luca, Vincenzo
In recent years, several studies have investigated genetic polymorphisms of antipsychotic drug-metabolizing enzymes and receptors. However, most studies focused on drug response and very few have investigated the genetic influence on antipsychotic dosage. The aim of the present study is to test the association between antipsychotic dosages at genome-wide level. The current dosage of antipsychotic medications was collected from 79 schizophrenia patients. The dosage was standardized using three different methods: chlorpromazine equivalent (CPZe), defined daily dose (DDD), and percentage of maximum dose (PM %). The patients were then genotyped using the Illumina HumanOmni2.5-8 BeadChip Kit. All markers were screened for significance using linear regression, and the p values were visualized using a Manhattan plot. The genome-wide analysis showed that the top Single-Nucleotide Polymorphisms (SNPs) associated with dosage variation were rs981975 on chromosome 14 for CPZe, rs4470690 on chromosome 4 for PM %, and rs79323383 on chromosome 8 for DDD. However, no genome-wide significantly associated SNPs were identified. In this pilot sample, we found promising trends for pharmacodynamic targets associated with antipsychotic dosage. Therefore, studies combining large prescription databases may identify genetic predictors to adjust the dose of antipsychotic medication.
Milne, Iain; Bayer, Micha; Cardle, Linda; Shaw, Paul; Stephen, Gordon; Wright, Frank; Marshall, David
Tablet is a lightweight, high-performance graphical viewer for next-generation sequence assemblies and alignments. Supporting a range of input assembly formats, Tablet provides high-quality visualizations showing data in packed or stacked views, allowing instant access and navigation to any region of interest, and whole contig overviews and data summaries. Tablet is both multi-core aware and memory efficient, allowing it to handle assemblies containing millions of reads, even on a 32-bit desktop machine. Tablet is freely available for Microsoft Windows, Apple Mac OS X, Linux and Solaris. Fully bundled installers can be downloaded from http://bioinf.scri.ac.uk/tablet in 32- and 64-bit versions.
Full Text Available Orally disintegrating systems have carved a niche amongst the oral drug delivery systems due to the highest compliance of the patients, especially the geriatrics and pediatrics. In addition, patients suffering from dysphagia, motion sickness, repeated emesis and mental disorders prefer these medications because they cannot swallow large quantity of water. Further, drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated in these dosage forms. However, the requirements of formulating these dosage forms with mechanical strength sufficient to withstand the rigors of handling and capable of disintegrating within a few seconds on contact with saliva are inextricable. The purpose of this research was to mask the bitter taste of granisetron hydrochloride. To mask the taste Kollicoat(r Smartseal 30D was used as coating polymer for pellet coating. The coated pellets of the drug was directly compressed with different superdisintegrant as AC-Di-Sol, Explotab and Kollidon CL in different concentration 5.0-7.5% w/w into an ODT. The prepared tablets were evaluated for hardness, friability, weight variation, wetting time, wet absorption ratio, in-vitro disintegration time and in vitro dissolution studies. Tablets exhibited quick disintegration characteristics with Kollidon CL in concentration 7.5% w/w i.e., within 20 seconds, which is characteristic of orally disintegrating dosage forms. More than 98% of drug was released from the formulations within 15 minutes. Formulations subjected to stability testing as per the ICH guidelines for 3 months, indicated stability with no change in taste, hardness, drug content, disintegration time and dissolution profiles. Thus, the results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated dosage forms in the oral cavity.
This work offers a re-edition of twelve mathematical tablets from the site of Tell Harmal, in the borders of present-day Baghdad. In ancient times, Tell Harmal was Šaduppûm, a city representative of the region of the Diyala river and of the kingdom of Ešnunna, to which it belonged for a time. These twelve tablets were originally published in separate articles in the beginning of the 1950s and mostly contain solved problem texts. Some of the problems deal with abstract matters such as triangles and rectangles with no reference to daily life, while others are stated in explicitly empirical contexts, such as the transportation of a load of bricks, the size of a vessel, the number of men needed to build a wall and the acquisition of oil and lard. This new edition of the texts is the first to group them, and takes into account all the recent developments of the research in the history of Mesopotamian mathematics. Its introductory chapters are directed to readers interested in an overview of the mathematical con...
Haznar-Garbacz, Dorota; Kaminska, Ewa; Zakowiecki, Daniel; Lachmann, Marek; Kaminski, Kamil; Garbacz, Grzegorz; Dorożyński, Przemysław; Kulinowski, Piotr
The presented work describes the formulation and characterization of modified release glassy solid dosage forms (GSDFs) containing an amorphous nifedipine, as a model BCS (Biopharmaceutical Classification System) class II drug. The GSDFs were prepared by melting nifedipine together with octaacetyl sucrose. Dissolution profiles, measured under standard and biorelevant conditions, were compared to those obtained from commercially available formulations containing nifedipine such as modified release (MR) tablets and osmotic release oral system (OROS). The results indicate that the dissolution profiles of the GSDFs with nifedipine are neither affected by the pH of the dissolution media, type and concentration of surfactants, nor by simulated mechanical stress of biorelevant intensity. Furthermore, it was found that the dissolution profiles of the novel dosage forms were similar to the profiles obtained from the nifedipine OROS. The formulation of GSDFs is relatively simple, and the dosage forms were found to have favorable dissolution characteristics.
Schiele, Julia T; Penner, Heike; Schneider, Hendrik; Quinzler, Renate; Reich, Gabriele; Wezler, Nikolai; Micol, William; Oster, Peter; Haefeli, Walter E
We evaluated the prevalence of difficulties swallowing solid dosage forms in patients with stroke-induced dysphagia and whether swallowing tablets/capsules increases their risk of penetration and aspiration. Concurrently, we explored whether routinely performed assessment tests help identify patients at risk. Using video endoscopy, we evaluated how 52 patients swallowed four different placebos (round, oval, and oblong tablets and a capsule) with texture-modified water (TMW, pudding consistency) and milk and rated their swallowing performance according to the Penetration Aspiration Scale (PAS). Additionally, Daniels Test, Bogenhausener Dysphagiescore, Scandinavian Stroke Scale, Barthel Index, and Tinetti's Mobility Test were conducted. A substantial proportion of the patients experienced severe difficulties swallowing solid oral dosage forms (TMW: 40.4 %, milk: 43.5 %). Compared to the administration of TMW/milk alone, the placebos increased the PAS values in the majority of the patients (TMW: median PAS from 1.5 to 2.0; milk: median PAS from 1.5 to 2.5, each p value <0.0001) and residue values were significantly higher (p < 0.05). Whereas video-endoscopic examination reliably identified patients with difficulties swallowing medication, neither patients' self-evaluation nor one of the routinely performed bedside tests did. Therefore, before video-endoscopic evaluation, many drugs were modified unnecessarily and 20.8 % of these were crushed inadequately, although switching to another dosage form or drug would have been possible. Hence, safety and effectiveness of swallowing tablets and capsules should be evaluated routinely in video-endoscopic examinations, tablets/capsules should rather be provided with TMW than with milk, and the appropriateness of "non per os except medication" orders for dysphagic stroke patients should be questioned.
Mitra, Amitava; Kesisoglou, Filippos; Dogterom, Peter
As part of the overall product development and manufacturing strategy, pharmaceutical companies routinely change formulation and manufacturing site. Depending on the type and level of change and the BCS class of the molecule, dissolution data and/or bioequivalence (BE) may be needed to support the change for immediate release dosage forms. In this report, we demonstrate that for certain weakly basic low-solubility molecules which rapidly dissolve in the stomach, absorption modeling could be used to justify a BE study waiver even when there is failure to show dissolution similarity under some conditions. The development of an absorption model for etoricoxib is described here, which was then used to a priori predict the BE outcome of tablet batches manufactured at two sites. Dissolution studies in 0.01 N HCl media (pH 2.0) had demonstrated similarity of etoricoxib tablets manufactured at two different sites. However, dissolution testing at pH 4.5 and pH 6.8 media failed to show comparability of the tablets manufactured at the two sites. Single simulations and virtual trials conducted using the 0.01 N HCl dissolution showed similarity in AUC and C max for all tablet strengths for batches manufactured at the two manufacturing sites. These predicted results were verified in a definitive bioequivalence study, which showed that both tablet batches were bioequivalent. Since the development of traditional in vitro-in vivo correlations (IVIVC) for immediate release (IR) products is challenging, in cases such as etoricoxib, absorption modeling could be used as an alternative to support waiver of a BE study.
Goyanes, Alvaro; Buanz, Asma B M; Hatton, Grace B; Gaisford, Simon; Basit, Abdul W
The aim of this study was to explore the potential of fused-deposition 3-dimensional printing (FDM 3DP) to produce modified-release drug loaded tablets. Two aminosalicylate isomers used in the treatment of inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA, mesalazine) and 4-aminosalicylic acid (4-ASA), were selected as model drugs. Commercially produced polyvinyl alcohol (PVA) filaments were loaded with the drugs in an ethanolic drug solution. A final drug-loading of 0.06% w/w and 0.25% w/w was achieved for the 5-ASA and 4-ASA strands, respectively. 10.5mm diameter tablets of both PVA/4-ASA and PVA/5-ASA were subsequently printed using an FDM 3D printer, and varying the weight and densities of the printed tablets was achieved by selecting the infill percentage in the printer software. The tablets were mechanically strong, and the FDM 3D printing was shown to be an effective process for the manufacture of the drug, 5-ASA. Significant thermal degradation of the active 4-ASA (50%) occurred during printing, however, indicating that the method may not be appropriate for drugs when printing at high temperatures exceeding those of the degradation point. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of the formulated blends confirmed these findings while highlighting the potential of thermal analytical techniques to anticipate drug degradation issues in the 3D printing process. The results of the dissolution tests conducted in modified Hank's bicarbonate buffer showed that release profiles for both drugs were dependent on both the drug itself and on the infill percentage of the tablet. Our work here demonstrates the potential role of FDM 3DP as an efficient and low-cost alternative method of manufacturing individually tailored oral drug dosage, and also for production of modified-release formulations. Copyright © 2014 Elsevier B.V. All rights reserved.
De Bruyne, Pauline; De Guchtenaere, Ann; Van Herzeele, Charlotte; Raes, Ann; Dehoorne, Jo; Hoebeke, Piet; Van Laecke, Erik; Vande Walle, Johan
Desmopressin 120 μg oral lyophilisate and 200 μg tablet are considered bioequivalent, based on extrapolation of studies in a limited number of adults and on one dose-finding study of desmopressin oral lyophilisate in children. However, no comparative pharmacokinetic study in children was executed confirming this statement. No data are available on the influence of food intake on the bioavailability of desmopressin tablet in a pediatric setting, although studies in adults have documented that food intake results in a significantly lower desmopressin plasma concentration. In this study, we analyzed plasma concentrations of desmopressin oral lyophilisate and tablet with concomitant food intake. Twenty-three children with monosymptomatic nocturnal enuresis (mean age, 12.7 years) were recruited. Two tests were performed on two separate days in identical conditions with a standardized food and fluid intake. Desmopressin was administered as desmopressin tablet or desmopressin oral lyophilisate immediately after a meal. Desmopressin plasma concentration was measured at 1 h, 2 h, and 6 h postdosing. No significant difference in plasma concentration of 120 μg desmopressin oral lyophilisate and 200 μg tablet was demonstrated, even with concomitant food intake. A significant difference in variability was found, identifying a smaller variance for desmopressin oral lyophilisate plasma concentrations at all time points. This study demonstrates comparable plasma levels for desmopressin oral lyophilisate, despite the lower dose. The dosage for desmopressin oral lyophilisate is more predictable due to the significantly smaller variance. Therefore, desmopressin oral lyophilisate seems more suitable, especially in the younger age group for which time interval between dinner and drug administration is limited.
Full Text Available Introduction: Rizatriptan benzoate is a potent and selective 5-HT1B/1D receptor agonist and is effective for the treatment of acute migraine. Difficulty in swallowing is common among all age groups, especially elderly and pediatrics. Orally disintegrating tablets may constitute an innovative dosage form that overcome the problem of swallowing and provides a quick onset of action. This study was aimed to formulate and evaluate an Orally Disintegrating Tablet (ODT containing Rizatriptan while using semi-synthetic and natural superdisintegrants. Methods: Orodispersible tablets were prepared by direct compression using natural superdisntegrant (Plantago ovata mucilage and semi-synthetic superdisntegrant (crospovidone. The prepared tablets were evaluated for hardness, friability, thickness, drug content uniformity, water absorption and wetting time. A 32 factorial design was used to investigate the effect of independent variables (amount of crospovidone and Plantago ovata mucilage on dependent variables [disintegration time, wetting time and Q5 (cumulative amount of drug release after 5 minutes]. A counter plot was also presented to graphically represent the effect of independent variable on the disintegration time, wetting time and Q5. The check point batch was also prepared to prove the validity of the evolved mathematical model. The systematic formulation approach helped in understanding the effect of formulation processing variable. Results: According to the results of optimized batches, the best concentration of superdisintegrant were as follows: 9.4 mg Psyllium mucilage and 8.32 mg crospovidone gave rapid disintegration in 35sec and showed 99% drug release within 5 minutes. Conclusion: Plantago ovata mucilage, a natural superdisintegrant, gives a rapid disintegration and high release when used with synthetic superdisntegrant in formulation of orally disintegrating tablet of Rizatriptan.
Full Text Available ABSTRACT The aim of this study was to evaluate binding potential of Mulva neglecta mucilage (MNM with subsequent comparison to PVP K30. Eight batches of Diclofenac sodium tablets were prepared by wet granulation technique keeping different concentrations (4, 6, 8 & 10% w/w of Mulva neglecta mucilage (extracted from leaves of Mulva neglecta and PVP K30 as standard binder. The granules of formulated batches showed bulk density (g/mL 0.49 ± 0.00 to 0.57 ± 0.00, tapped density (g/mL 0.59 ± 0.01 to 0.70 ± 0.01, Carr's index 09.27 ± 0.95 to 19.65 ± 0.59, Hausner's ratio 1.12 ± 0.00 to 1.24 ± 0.01 and angle of repose 30.37 ± 2.90 °C to 36.86 ± 0.94 °C. Tablets were compressed to hardness 7.50 to 7.95 kg/cm2. The tablets showed 0.39 ± 0.02 to 0.39 ± 0.01% friability and 7:20 to 14:00 min disintegration time. Granules and post-compression evaluation revealed that parameters assessed were all found to be within the pharmacopoeial limits. The results (hardness, disintegration and dissolution proved that Mulva neglecta mucilage has better binding capacity for preparation of uncoated tablet dosage form as compared to PVP K30. Among all the formulations, MN-1 to MN-4 showed slow release as compared to PV-1 to PV-4 and thereby Mulva neglecta mucilage exhibited satisfactory drug release phenomenon tablets of diclofenac sodium.
Wang, Lei; Tang, Xing
Bioadhesive tablet formulations of ketoconazole for vaginal delivery were studied. Carbomer (Carbopol 974P, Carbopol 934P), hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) were used as candidate bioadhesive polymers. Effervescent was incorporated into the formulations as a disintegration agent. The swelling behavior and bioadhesive strength of the drug-free tablets were investigated. Carbopol 934P was selected as biopolymer in combination with HPMC or HPC at different ratios to develop five drug-loaded formulations. The swellings, tackiness and in vitro release were studied on the tablets. A good sustained effect and a moderate bioadhesion were obtained with the tablets. The formulation containing 100mg of effervescent, with the Carbopol 934P:HPC ratio of 1:9, seemed to be the optimum one for the tablet. In vivo drug residence tests were carried out by administering the preferred formulation to female rats. The results showed that the drug remaining followed a one-order model. Even after 24h of administration in vagina of rats, 17% of the original employed drug was retained on the vaginal tissue. Our study may provide a potential vaginal tablet formulation of ketoconazole against Candida albicans.
Full Text Available The present investigation is concerned about the development of floating bioadhesive drug delivery system of venlafaxine hydrochloride which after oral administration exhibits a unique combination of floating and bioadhesion to prolong gastric residence time and increase drug bioavailability within the stomach. The floating bioadhesive tablets were prepared by the wet granulation method using different ratios of hydroxypropyl methyl cellulose (HPMC K4MCR and Carbopol 934PNF as polymers. Sodium bicarbonate (NaHCO3 and citric acid were used as gas (CO2 generating agents. Tablets were characterized for floating properties, in vitro drug release, detachment force, and swelling index. The concentration of hydroxypropyl methyl cellulose and Carbopol 934PNF significantly affects the in vitro drug release, floating properties, detachment force, and swelling properties of the tablets. The optimized formulation showed the floating lag time 72±2.49 seconds and duration of floating 24.50±0.74 hr. The in vitro release studies and floating behavior were studied in simulated gastric fluid (SGF at pH 1.2. Different drug release kinetics models were also applied. The in vitro drug release from tablets was sufficiently sustained (more than 18 hr and the Fickian transports of the drug from the tablets were confirmed. The radiological evidence suggests that the tablets remained buoyant and altered position in the stomach of albino rabbit and mean gastric residence time was prolonged (more than > 6 hr.
Sildenafil citrate tablets (VIAGRA; Pfizer Inc) have been used since 1998 as an oral therapy for the treatment of erectile dysfunction. However, in some cases, patients may have difficulty in swallowing tablets, and the need to use water to aid in the oral administration of the tablets has the potential to interrupt the sexual encounter, reduce spontaneity, and therefore decrease the quality of the experience. Two oral soluble film (OSF) formulations of sildenafil were developed using MonoSol Rx's proprietary PharmFilm technology. Both films were formulated to dissolve rapidly on the tongue, thereby releasing the drug into the oral cavity, whereupon it is swallowed without the use of water. From a patient perspective, it is anticipated that the film formulations of sildenafil citrate will provide a more compliant and discreet dosage form. The purpose of this clinical study was to compare the bioequivalence of the 2 sildenafil OSF 100 mg formulations (MonoSol Rx, LLC) with the sildenafil citrate 100 mg tablets. The design was a single-dose, randomized, open-label, 3-period, 6-sequence, 3-treatment, single-center, crossover study conducted in 18 healthy, nonsmoking male volunteers under fasting conditions, with each treatment period separated by a 7-day washout period. Plasma sildenafil concentrations were measured predose and then periodically to 24 hours after dosing. The 90% confidence intervals for plasma sildenafil AUC0-t, AUC0-∞, and Cmax for both sildenafil OSF formulations as compared with sildenafil citrate tablets were all within the 80%-125% range, indicating bioequivalence of both film formulations to sildenafil citrate tablets. Overall, the demonstrated bioequivalence coupled with the performance advantages of an OSF dosage form (ie, rapid dissolution in the mouth, can be taken without water, and can be dosed discreetly) suggest that the sildenafil OSF may provide an attractive alternative to sildenafil citrate oral tablets.
Akin-Ajani, Olufunke D; Itiola, Oludele A; Odeku, Oluwatoyin A
The effects of plantain starch obtained from the unripe fruit of the plant Musa paradisiaca L. (Musaceae) on the mechanical and disintegration properties of paracetamol tablets have been investigated in comparison with the effects of corn starch BP using a 2(3) factorial experimental design. The individual and combined effects of nature of starch binder (N), concentration of starch binder (C), and the relative density of tablet (RD) on the tensile strength (TS), brittle fracture index (BFI), and disintegration time (DT) of the tablets were investigated. The ranking of the individual effects on TS was RD > C > N, on BFI was C > RD > N and on DT was N > C > RD. The ranking for the interaction effects on TS and DT was N-C > N-RD > C-RD, while that on BFI was N-C > C-RD > N-RD. Changing nature of starch from a "low" (plantain starch) to a "high" (corn starch) level, increasing the concentration of starch binding agent from 2.5% to 10.0% wt/wt, and increasing relative density of the tablet from 0.80 to 0.90, led to increase in the values of TS and DT, but a decrease in BFI. Thus, tablets containing plantain starch had lower tensile strength and disintegration time values than those containing corn starch, but showed better ability to reduce the lamination and capping tendency in paracetamol tablet formulation. The interaction between N and C was significantly (P < .001) higher than those between N and RD and between C and RD. There is therefore the need to carefully choose the nature (N) and concentration (C) of starch used as binding agent in tablet formulations to obtain tablets of desired bond strength and disintegration properties. Furthermore, plantain starch could be useful as an alternative binding agent to cornstarch, especially where faster disintegration is required and the problems of lamination and capping are of particular concern.
Chakravarty, Paroma; Suryanarayanan, Raj; Govindarajan, Ramprakash
The objective of this article was to monitor phase transformation in thiamine hydrochloride, from a nonstoichiometric hydrate (NSH) to a hemihydrate (HH), in stored tablets, prepared both by direct compression and wet granulation, and to relate the storage-induced phase transformation with changes in tablet microstructure, physical properties, and performance. Raman spectroscopy revealed complete NSH → HH transformation in tablets, within 30 h of storage at 40°C/75% relative humidity. When the tablets were prepared by wet granulation of NSH alone, there was a marked increase in both tablet volume and hardness on storage. However, when microcrystalline cellulose (MCC) was included in granulation, the resulting stored tablets also exhibited a pronounced increase in disintegration time. In contrast, tablets prepared by dry processing via compression of a NSH-MCC physical mixture did not exhibit any changes in properties, despite the in situ solid form conversion. Scanning electron microscopy revealed growth of needle-like HH crystals in all stored tablets and mercury porosimetry revealed considerable changes in the pore size distribution during storage. Longer storage led to crystal growth (Ostwald ripening), causing further gradual but less dramatic changes in properties. The phase transformation and the complex interparticulate associations in the tablet influenced the changes in tablet microstructure, compact physical properties, and product behavior. Copyright © 2011 Wiley Periodicals, Inc.
the development of a method for the control of polyelectrolyte dosage were sug- gested. They were: " Sedimentation Potential " Turbidity Titration ... potentiometrically in accordance with Standard Method (1975) where 50 ml samples were titrated to a pH of 4.5 by addition of 0.02 N sulfuric acid. Results were...into the sample via a titration buret to give a desired concentration. (3) Water sample was allowed to mix with polyelectrolyte for 10 to 15 second
The effects of the excipients on tablet hardness, friability, disintegration and dissolution rate were also evaluated. Tablets containing 3 - 4 % w/w STEAROLAC-S gave unit ejection force values comparable to those of tablets containing 2% w/w magnesium stearate. Tablets containing 4% STEAROLAC-S exhibited better ...
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Aminopropazine fumarate tablets. 520.82a Section... Aminopropazine fumarate tablets. (a) Specifications. The drug is in tablet form. Each tablet contains aminopropazine fumarate equivalent to 25 milligrams of aminopropazine base. (b) Sponsor. See No. 000061 in § 510...
Shirsand, S B; Suresh, Sarasija; Swamy, P V; Para, M S; Nagendra Kumar, D
In the present work, fast disintegrating tablets of prochlorperazine maleate were designed with a view to enhance patient compliance by direct compression method. In this method, crospovidone (up to 3% w/w) and croscarmellose sodium (up to 5% w/w) in combination were used as superdisintegrants. Since disintegrants complement each other, accelerating the disintegration process when used together. Estimation of prochlorperazine maleate in the prepared tablet formulations was carried out by extracting the drug with methanol and measuring the absorbance at 254.5nm. The prepared formulations were further evaluated for hardness, friability, drug content uniformity, in vitro dispersion time, wetting time and water absorption ratio. Based on in vitro dispersion time (approximately 12 s), one promising formulation was tested for in vitro drug release pattern in phosphate buffer pH 6.8 and short-term stability (at 40 degrees /70% RH for 3 mo), drug-excipient interaction (IR spectroscopy) were studied. Among the formulations tested, formulation DCPC(4) containing 5% w/w of croscarmellose sodium and 3% w/w of crospovidone as superdisintegrant emerged as the overall best (t(50%) 7.0 min) based on drug release characteristics in pH 6.8 phosphate buffer compared to commercial conventional tablet formulation (t(50%) 17.4 min). Short-term stability studies on the promising formulation indicated that there were no significant changes in drug content and in vitro dispersion time (p<0.05).
K. H. Janardhana
Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Cambendazole oral dosage forms. 520.300 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.300 Cambendazole oral dosage forms. ...
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Febantel oral dosage forms. 520.903 Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.903 Febantel oral dosage forms. ...
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Phenylbutazone oral dosage forms. 520.1720 Section... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1720 Phenylbutazone oral dosage forms. ...
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Diethylcarbamazine citrate oral dosage forms. 520... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.622 Diethylcarbamazine citrate oral dosage forms. ...
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Sulfamethazine sodium oral dosage forms. 520.2261... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.2261 Sulfamethazine sodium oral dosage forms. ...
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chlortetracycline oral dosage forms. 520.445... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.445 Chlortetracycline oral dosage forms. ...
... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline injectable dosage forms. 522.1660... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1660 Oxytetracycline injectable dosage forms. ...