Some Factors Affecting the Release of Drug from Membrane Coated Slow Release Tablets

Tablets containing sodium salicylate were prepared by direct compression and coated with ethylcellulose and polyethylene glycol 3350. The effect of drug loading, direct compression carrier type, polymer ratio in the coating solution, pH of the dissolution medium, and agitation speed on the drug release were investigated using the USP XXI paddle method. It was observed that direct compression carriers, ratio of ethyl cellulose to polyethylene glycol, the amount of drug present in the tablet, and agitation speed used did not have any influence on the drug release from coated tablets, while the pH of the dissolution medium (gastric vs. intestinal fluids) was found to affect the drug release.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^-2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Abstract

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^?2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Factors Influencing Capping and Cracking of Mefenamic Acid Tablets

The tendency of capping and longitudinal cracks of mefenamic acid tablets was evaluated in relation to the amount of the binder, the influence of the granulation technique, and the relative humidity of the granules. Tablets made from fluidized bed granules using methylcellulose in the granulating liquid showed significantly lower capping and longitudinal cracks than tablets from conventional granules prepared by wet granulation using methylcellulose as a dry binder.     

Role of Surfactant on Drug Release from Tablets

The addition of a surfactanat into a tablet formulation appears to be attractive method of improve the drug release rate. The improved release rate is often associated with the effect of surfactant increasing the hydrophilicity of the dosage form thereby promoting drug dissolution. The findings of this investigation showed tha the presence of surfactant infulenced the tablet disintegration rate, producing a finer dispersion of disintergrated particles. It follows that the action of surfactant improving drug dissolution from tablets may be attributed ot the aciton of surfactnat producing fine disintegrated particles with correspondingly larger surface area for drug dissolution. It was also demonstrated that upon tablet disintergration the disinstegrated particles have a tri-moal frequency distribution.     

Release of Acetazolamide from Swellable Hydroxypropylmethylcellulose Matrix Tablets

Controlled-release swellable tablets were prepared by a simple direct compression process using hydroxypropylmethylcellulose (HPMC) as the matrix former. The effects of the viscosity and concentration of the polymer and the pH of the dissolution medium on the release behavior of acetazolamide were investigated. The influence of the drug particle size was also evaluated. Ten, 15, 20, and 25% of two different viscosity grades of HPMC were dry mixed with acetazolamide, Fast Flo Lactose, and magnesium stearate, then directly compressed into tablets. The experimental tablets were tested for their drug contents, weight variations, and hardnesses. Dissolution tests were carried out under sink conditions at three different pH values: pH 1.2, 5.4, and 7.4. Release rate data were evaluated according to the equation log M/M_w = log k + n log t.     

Release of Acetazolamide from Swellable Hydroxypropylmethylcellulose Matrix Tablets

Abstract

Controlled-release swellable tablets were prepared by a simple direct compression process using hydroxypropylmethylcellulose (HPMC) as the matrix former. The effects of the viscosity and concentration of the polymer and the pH of the dissolution medium on the release behavior of acetazolamide were investigated. The influence of the drug particle size was also evaluated. Ten, 15, 20, and 25% of two different viscosity grades of HPMC were dry mixed with acetazolamide, Fast Flo Lactose, and magnesium stearate, then directly compressed into tablets. The experimental tablets were tested for their drug contents, weight variations, and hardnesses. Dissolution tests were carried out under sink conditions at three different pH values: pH 1.2, 5.4, and 7.4. Release rate data were evaluated according to the equation log M/M_w = log k + n log t.     

Testing of Drug Release from Bioadhesive Vaginal Tablets

Abstract

To establish en in vitro test method that can predict the drug release and dissolution behaviour of vaginal bioadhesive controlled release tablets, a system was developed and its appropriateness to the in situ conditions was examined. For this purpose, the dissolution rates of vaginal bioadhesive tablets were measured by three different methods. These were, USP dissolution apparatus two and a new vaginal dissolution tester (NVDT) which was developed by us with some modification of the vaginal tablet desentegration apparatus of BP 1988 and, testing in cow vaginas in situ. Four different bioadhesive tablet formulations were used being composed of the drug and the anionic polymer, polyacrylic acid (PAA) and the nonionic polymers, hydroxypropylmethyl cellulose (HPMC) and ethyIcellulose (EC). The release profiles of the in vitro and in situ methods were investigated and evaluated kinetically.

It was found that NVDT could be used to investigate the drug release from vaginal tablets.     

Role of Surfactant on Drug Release from Tablets

Abstract

The addition of a surfactanat into a tablet formulation appears to be attractive method of improve the drug release rate. The improved release rate is often associated with the effect of surfactant increasing the hydrophilicity of the dosage form thereby promoting drug dissolution. The findings of this investigation showed tha the presence of surfactant infulenced the tablet disintegration rate, producing a finer dispersion of disintergrated particles. It follows that the action of surfactant improving drug dissolution from tablets may be attributed ot the aciton of surfactnat producing fine disintegrated particles with correspondingly larger surface area for drug dissolution. It was also demonstrated that upon tablet disintergration the disinstegrated particles have a tri-moal frequency distribution.     

Testing of Drug Release from Bioadhesive Vaginal Tablets

To establish en in vitro test method that can predict the drug release and dissolution behaviour of vaginal bioadhesive controlled release tablets, a system was developed and its appropriateness to the in situ conditions was examined. For this purpose, the dissolution rates of vaginal bioadhesive tablets were measured by three different methods. These were, USP dissolution apparatus two and a new vaginal dissolution tester (NVDT) which was developed by us with some modification of the vaginal tablet desentegration apparatus of BP 1988 and, testing in cow vaginas in situ. Four different bioadhesive tablet formulations were used being composed of the drug and the anionic polymer, polyacrylic acid (PAA) and the nonionic polymers, hydroxypropylmethyl cellulose (HPMC) and ethyIcellulose (EC). The release profiles of the in vitro and in situ methods were investigated and evaluated kinetically.

It was found that NVDT could be used to investigate the drug release from vaginal tablets.     

Release of Cyclobenzaprine Hydrochloride from Osmotically Rupturable Tablets

ABSTRACT

Osmotically rupturable systems were developed and the release of cyclobenzaprine hydrochloride (model drug) from the systems was investigated. Systems were designed using mannitol (osmotic agent) and increasing amounts of polyethylene oxide (PEO, a water-swellable polymer) surrounded by a semipermeable membrane. When placed in an aqueous environment, osmotic water imbibition into the systems distended and swelled the systems until the membrane ruptured and released the active compound to the outside environment. Tablets with increasing amount of PEO exhibited longer rupture times. This may be due to osmotic pressure-modulating properties of the polymer, changing the rate of water imbibition into the systems.

The integrity of the membranes was investigated using high-pressure mercury intrusion porosimetry. Minimal mercury intrusion into the membrane structure and core tablet indicated membrane integrity and lack of defective areas or pinholes. The results were in agreement with the release profiles where no drug release was detected prior to membrane rupture. Mercury intrusion porosimetry appears to be a promising technique for evaluation of membrane integrity.

Once the systems ruptured, drug was released by osmotic pumping and diffusion mechanisms through the ruptured area. There was a decrease in drug release rate with inclusion of PEO in the core.

The effects of film thickness on rupture and release times were also investigated. Devices with thicker films produced longer rupture times. This is in agreement with the theoretical prediction.     

Natural Polymer Hydrophilic Matrix: Influencing Drug Release Factors

In porous hydrophilic polymeric systems, two phenomena control the release of drugs: the water uptake and polymer swelling.

Directly compressed hydrophilic matrices were prepared with scleroglucan as gelling agent. A principal components analysis enables the authors to study the correlation between the above phenomena and the dissolution behavior in order to interpret the effect of polymer concentration, excipient solubility and compression force on the drug release.     

Natural Polymer Hydrophilic Matrix: Influencing Drug Release Factors

In porous hydrophilic polymeric systems, two phenomena control the release of drugs: the water uptake and polymer swelling.

Directly compressed hydrophilic matrices were prepared with scleroglucan as gelling agent. A principal components analysis enables the authors to study the correlation between the above phenomena and the dissolution behavior in order to interpret the effect of polymer concentration, excipient solubility and compression force on the drug release.     

Effect of Polysorbates on Atenolol Release from Film-Coated Tablets

The effects of different concentrations of various polysorbates on the release rate of atenolol from film-coated tablets were evaluated. The release profile of atenolol showed that increasing the concentration of polysorbate resulted in an increase in the release rate of atenolol. The type of polysorbate had less effect on the release rate of atenolol. This study revealed that the release kinetic of atenolol from these film-coated tablets was a function of polysorbate concentration. Correlation coefficients of kinetic models could not solely determine the suitability of the models; the sum of the least square of differences also should be calculated when different kinetic models have similar correlation coefficients.     

影响二氧化硅还原氮化的几个动力学因素

本文对 SiO_2-C-N_2反应体系进行了催化剂的探索,研究了温度(1250～1450℃)、时间(5～30h)、气氛(N_2或 N_2+H_2)和晶种等因素对氮化结果的影响。试验表明:催化剂还原铁粉的加入能加速氮化反应的进行,随着加入量的增加其氮化率有一最大值;温度升高、少量 H_2和晶种的引入,氮化率都有不同程度的增加;当恒温时间τ<25h 时,氮化率随时间延长而增加,反之,τ>25h 时,氮化率随时间延长而减少。另外,产物中结合碳随着催化剂和晶种的引入而减少,随着 H_2的引入,氮化温度的升高和恒温时间的过长而增加;产物的形貌也因原料和气氛的改变而变化。     

Sustained Release Tablets of Theophylline

Sustained release tablets of theophylline (anhydrous) were prepared using hydrophilic polymers (Methyl Cellulose, Methocel K₄M and K₁₅M) and hydrophobic polymers (ethyl cellulose, cellulose acetate). In addition water soluble adjuvants were used to modify release rate. With methocel, rapid gelling was observed and release was near zero-order, whereas with hydrophobic polymers release followed Fickian law of diffusion.     

Sustained Release of Theophylline from Eudragit RLPO and RSPO Tablets

Abstract

Newer polymeric grades of Eudragit, RLPO and RSPO, were explored for their utilities by formulating a sustained-release tablet of theophylline as a model drug. Formulations selected on the basis of their lower polymer content and drug release content, over the period of 12 hr, were compared with the marketed formulation. These were evaluated for dissolution characteristics. In vitro release showed zero-order kinetics (r = 0.9879-0.994.5; p < 0.001). In vivo evaluations were carried out on healthy human volunteers (23 ± 2.68 years old; 48.64 ± 6.31 kg). Dissolution rate constant (k), C_max, T_max, AUC_0-12, AUC_0-24, and t_1/2 were evaluated statistically by two-way ANOVA. Upon t test, a highly significant difference between test products and the marketed product was observed. Wagner-Nelson analysis of the in vivo data revealed controlled-release absorption profiles for selected formulations. Linear regression analysis of the mean % of dose absorbed versus mean in vitro release, resulted in statistically significant correlation. Coefficient of correlation values between AUC_0-12 and k, and AUC_0-24 and k were found to be 0.991 (p < 0.01) and 0.984 (0.01 < p < 0.05), respectively. These data support a level-A correlation between in vitro release rate profiles and the in vivo absorptions for theophylline.     

高温持久试验的若干影响因素

结合多年的实践经验,概括介绍了高温持久试验过程中对试验结果有影响的各种故障因素,出现故障时的原因分析,并提出了切实可行的预防措施,以确保试验结果的准确性和可靠性。     

Investigation of Hypromellose Particle Size Effects on Drug Release from Sustained Release Hydrophilic Matrix Tablets

Selected combinations of six model drugs and four hypromellose (USP 2208) viscosity grades were studied utilizing direct compression and in vitro dissolution testing. Experimental HPMC samples with differing particle size distributions (coarse, fine, narrow, bimodal) were generated by sieving. For some formulations, the impact of HPMC particle size changes was characterized by faster drug release and an apparent shift in drug release mechanism when less than 50% of the HPMC passed through a 230 mesh (63 μm) screen. Within the ranges studied, drug release from other formulations appeared to be unaffected by HPMC particle size changes.     

Role of Cellulose Ether Polymers on Ibuprofen Release from Matrix Tablets

Cellulose derivatives are the most frequently used polymers in formulations of pharmaceutical products for controlled drug delivery. The main aim of the present work was to evaluate the effect of different cellulose substitutions on the release rate of ibuprofen (IBP) from hydrophilic matrix tablets. Thus, the release mechanism of IBP with methylcellulose (MC25), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K15M or K100M) was studied. In addition, the influence of the diluents lactose monohydrate (LAC) and β-cyclodextrin (β-CD) was evaluated. Distinct test formulations were prepared containing: 57.14% of IBP, 20.00% of polymer, 20.29% of diluent, 1.71% of talc lubricants, and 0.86% of magnesium stearate as lubricants. Although non-negligible drug-excipient interactions were detected from DSC studies, these were found not to constitute an incompatibility effect. Tablets were examined for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, swelling, and dissolution performance. Polymers MC25 and HPC were found to be unsuitable for the preparation of this kind of solid dosage form, while HPMC K15M and K100M showed to be advantageous. Dissolution parameters such as the area under the dissolution curve (AUC), the dissolution efficiency (DE_{20 h}), dissolution time (t 50%), and mean dissolution time (MDT) were calculated for all the formulations, and the highest MDT values were obtained with HPMC indicating that a higher value of MDT signifies a higher drug retarding ability of the polymer and vice-versa. The analysis of the drug release data was performed in the light of distinct kinetic mathematical models—Kosmeyer-Peppas, Higuchi, zero-, and first-order. The release process was also found to be slightly influenced by the kind of diluent used.