Compound Metformin/Glipizide Bilayer Extended Release Tablets: Development and in Vitro Release

Aim In this study, compound metformin/glipizide bilayer extended release tablets were formulated with hydroxypropyl methylcellulose （HPMC） by wet granulation technique in order to tackle the problems associated with the muhidrug therapy of non-insulin dependent diabetes mellitus. Me^ls High-dose metformin is difficult to formulate into a tablet dosage form due to its poor compressibility and compactibility. In this study, the way to overcome the difficulty was to utilize stearic alcohol to prepare the tablet formulation. The influences of viscosity, amount of HPMC, and weight of fillers were investigated. The optimal formulation had acceptable physicochemical properties and released metformin and glipizide over 10 h. Results The data of metformin obtained from in vitro release fitted Higuchi kinetics best, while the release of glipizide in vitro was found to follow zero kinetics. Conclusion Compound metformin/glipizide bilayer extended release tablets have been successfully developed.

Study of Sustained Release Phenylpropanolamine Hydrochloride Hydrophilic Matrix Tablets Containing Hydroxypropylmethylcellulose K100M and Carbopol 971P

选用HPMC K100M和卡波普971P为骨架材料，粉末直接压片法制备骨架片，考察释放度，反相高效液相色谱法检测盐酸苯丙醇胺（PPA·HCl）的浓度。释药曲线均符合Higuchi方程（R＞0．98，P＜0．01）。运用正交设计法，以美国市场的PPA·HCl缓释片Acutrim^R为对照，相似因子f2值为指标，筛选获得了最优处方。其工艺重现性合格。研制片在0．1mol·L^-1 HCl,H2O(pH6.5)，磷酸盐缓冲液（PBS）pH5.0,6.8和7.4的介质中，以及在0.1mol·L^-1HCl中释放2h，转移至PBS6．8中释放10h，相对于对照品的f2值为63－74，表明在各介质中两制剂的释药曲线相似。释药影响因素的考察结果表明：在本实验考察的范围内，骨架片在水中的释药速率与HPMC K100M和卡波普971P的用量呈负相关。HPMC K100M和卡波普971P的比例（保持聚合物总用量相同），硬脂酸镁量和骨架片硬度对释药速率无显著性影响。

Pharmacokinetics of Moclobemide Sustained Release Tablets after Multiple Oral Dose Administration in Healthy Volunteers

To investigate the pharmacokinetic characteristics of moclobemide sustainedrelease tablets after multiple oral dose administration in healthy Chinese volunteers. MethodsMoclobemide sustained release tablets were given as a multiple oral dose regimen of 300 mg oncedaily for five consecutive days to 12 healthy volunteers. The concentrations of moclobemide inplasma were determined by reversed-phase high performance liquid chromatography. The partialpharmacokinetic parameters were calculated using 3p97 pharmacokinetic program. Results Theconcentration-time profile fitted an one-compartment model best. The steady-state pharmacokineticparameters of moclobemide sustained release tablets after multiple oral doses were as follows:C_(max) was (1 950 +- 156) μg· L^(-1), T_(max) was (6.00 +-1.55) h, T_(1/2(kel)) was (3.14 +-0.12)h, AUC_(ss 0-24) was (22 836 +- 1 842) μg·h· L^(-1), MRT was (7.68+-0.36) h, CL/F_((s)) was(20.2+-2.1) L·h^(-1), and V/F_((c)) was (91.4+-9.4) L, respectively. No marked adverse events werenoted during this study. Conclusion The formulation has a sustained-release effect and goodtolerance in the healthy volunteers, which provides useful information for clinical practice.

Pharmacokinetics of Controlled Release and Immediate Release Morphine Sulphate Tablets after a Single Dose and Multiple Doses in Chinese Volunteers

The pharmacokinetics of morphine sulphate was studied in 10 Chinese healthy volunteers after a single oral dose. Blood samples were collected before and after administration of controlled release tablets (CRMS, 30 mg) and immediate release tablets (IRMS, 20 mg). The plasma concentration of morphine was determined by GC MS. The pharmacokinetic parameters of controlled release tablets and immediate release tablets were calculated∶ C max was 19.38±3.80 and 21.27±6.21 ng/ml, t max was 2.36 ±0.37 h and 0.56±0.16 h, t 1/2β was 3.53±0.87 and 3.03±0.74 h, AUC was 145.15±17.65 and 93.08±16.65 ng/ml, respectively. The steady state plasma concentration of morphine sulphate in cancer patients after multiple doses was achieved, C max of CRMS and IRMS was 27.43±0.33 ng/ml and 22.68±0.16 ng/ml, C min of CRMS and IRMS was 19.45±1.44 ng/ml and 18.14±0.49 ng/ml, respectively.

Tablets of paliperidone using compression-coated technology for controlled ascending release

The aim of this work was to prepare ascending release compression-coated(CC) tablets with paliperidone(PAL) using a simple manufacturing technique and short manufacturing process.The release behavior and mechanisms in vitro of the final tablets was investigated and evaluated. The PAL CC tablets were comprised of a core layer of high viscosity hydroxypropyl cellulose(HPC-H) and a coating layer of high viscosity hydroxypropyl methylcellulose(HPMCK100 M). Several factors such as materials and core tablet compositions were studied for their influence in the formulation procedure. The drug release mechanism was studied using gravimetric analysis. The data could be fitted to the Peppas model. The ascending drug release results were expressed in terms of the slope of the release curve at different time points.Results showed that the formulation could achieve a good ascending drug release when the weight ratio of PAL was 5:1(core:layer). The fraction of HPC and HPMC was 33 %, and the combination of Eudragit RL-PO was 10%. The ascending release mechanism was due to solvent penetration into the PAL CC tablets, and subsequent drug dissolution from the gelatinous HPC and HPMC matrix erosion. The release mechanism was therefore a combination of diffusion and erosion. This work demonstrated that the compression-coated tablets could achieve controlled ascending release over 24 h for the oral administration systems.

Monolithic LC method applied to fesoterodine fumarate low dose extended-release tablets:Dissolution and release kinetics

A dissolution test for fesoterodine low dose extended-release tablets using liquid chromatographic（LC） method equipped with a C18 monolithic column was developed and validated. LC system was operated isocratically at controlled temperature（40 1C） using a mobile phase of acetonitrile：methanol：0.03 M ammonium acetate（p H 3.8）（30：15：55, v/v/v）, run at a flow rate of 1.5 m L/min and detected at 208 nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2（paddle） at 100 rpm and 900 m L of phosphate buffer at p H 6.8 as the dissolution medium.Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.

Preparation and <i>in Vitro</i>Drug Release Evaluation of Once-Daily Metformin Hydrochloride Sustained-Release Tablets

The objective of this study was to develop once-daily metformin hydrochloride sustained-release tablets (MHSRT) and evaluate their in vitro release behavior. MHSRT were prepared by the film coating method. The in vitro drug release rate of MHSRT and the commercial tablets Fortamet? made in the United States of America in water was fitted with zero order kinetic equation, and Ritger-Peppas kinetic equation in 0.1 M HCl and pH 6.8-phosphate buffer, respectively. The similarity factor f2 values of MHSRT in three different dissolution medium were 82, 80 and 74, respectively in comparison with imported Fortamet?, which were all greater than 50. The results of storage-stability showed that MHSRT were stable for at least 6 months under stress condition (40℃ ± 2℃, RH 75% ± 5%). Therefore, in this study, MHSRT were successfully prepared using optimized formulation technologies that meet mass produce. The in vitro release behavior of MHSRT was almost similar to that of imported Fortamet?.

Extended tacrolimus release via the combination of lipid-based solid dispersion and HPMC hydrogel matrix tablets

The objective of this study is to evaluate the feasibility of obtaining extended release of tacrolimus by a novel combination of lipid-based solid dispersion and matrix-type extended release tablet techniques. Tacrolimus solid dispersion was prepared using glycerylbehenate(Compritol~?ATO888) and Pluronic F127 as the carrier materials with hot-melt method, which was then blended with hydrogel matrix materials, such as HPMC and lactose, the powders were directly compressed into tablets. In vitro drug release tests were carried out to evaluate the performance of the solid dispersions and the tablets. The dissolution rate of tacrolimus was significantly improved by the lipid-based solid dispersion, and the incorporation of HPC into the solid dispersion obviously improved its stability after storage. Extended release tablets loaded with tacrolimus solid dispersion showed prolonged drug release patterns over 24 h, the release patterns of the tablets can be tailored by the compositions of the matrix materials, including the types and content of HPMCs. A modified processing method that directly mixed the melted solid dispersion with HPMC powders improved the uniformity of the solid dispersion inside the tablet matrix and release profile. The release data of the extended release tablet fitted well to the Korsmeyer–Peppas model with n value of 0.85, which suggested diffusion-and erosion-controlled release mechanism. The combination of lipid-based solid dispersion and HPMC hydrogel matrix may find wide applications in the extended release dosage forms of high potent, water-insoluble drugs.

HPLC Method for the Determination of Tamsulosin Hydrochloride in Sustained Release Tablets

The development and validation of an isocratic high performance liquid chromatographic method is described for the determination of tamsulosin hydrochloride in sustained release tablets. The determination was performed on a Diamonsil BDS C18 column with a mobile phase consisting of a mixture of acetonitrile, methanol and 0 5% phosphoric acid solution (20∶30∶50, V/V/V ) at a flow rate of 1 0 mL/min. UV detection was made at 274 nm. The linear range for tamsulosin hydrochloride was 0 81-8 10 μg/mL. The mean recovery was 99 8% ( S R=0 7%, n =9), and the precision was found to be 0 45% ( n =9). The proposed method can be used for routine analysis of tamsulosin hydrochloride in sustained release tablets.

Development and bioequivalence study of potassium chloride extended release tablets

The purposes of this study are to prepare the generic extended release tablet of potassiumchloride(PC) 600 mg and to compare the absorption of potassium ion from the experimen-tal tablets to that of Kaleorid? LP 600 mg(Leo Pharmaceutical Products, Denmark). Car-nauba wax was used as retardant in the matrix core tablets. The core tablets were coatedwith blends of ethyl cellulose(EC) and hydroxypropyl methyl cellulose(HPMC) to modulatethe drug release. Results of a selective two-level, three-factor experiment design revealedthat a blend of 41.75% of EC and 58.25% of HPMC at 4.5% weight gained could produce thecoated tablets having dissolution profiles similar to those of Kaleorid?. A two-treatment,two-period, two-sequence crossover bioequivalence study was carried out on 24 healthyvolunteers to compare the absorption of potassium ion from experimental tablets to thatfrom Kaleorid?. The potassium ion in the urine was measured by a selective electrode of theADVIA 1650 system(Bayer) and used to calculate cumulative urinary excretion and urinaryexcretion rate. Results of 90 percent confidence interval analysis showed that the limits fornatural log-transformed cumulative urinary potassium excretion(Ln Ae 0-24) of test productwere in the range of 3.73–3.79 mEq, corresponding to 99.08%–100.92% of Kaleorid ?, respec-tively, and the limits for natural log-transformed maximal potassium excretion rate( R max) oftest product were in the range of 1.72–1.82 mEq/h, corresponding to 97.34%–102.66% of refer-ence product, respectively. Both of them fell within the bioequivalence interval(80%–125%)of reference product, proving that experimental product is bioequivalent to Kaleorid ?.

Carobomer Based Controlled Release Designs of Atorvastatin Calcium Tablets Evaluated Using Quality by Design (QbD) Approach

The study carried out here was focused on developing conventional monolithic controlled release matrix tablet of Atorvastatin calcium using carbomer as release controlling polymer. This system ensures the drug release at the alkaline pH region where the drug has got maximum solubility. Further the study was concentrated on comparing the impact of gelling agent polyvinyl pyrrolidone on drug release. Quality by design tools were considered during formulation development and the polymer concentrations were optimized adopting the statistical tool, design of experiments (DoE). The optimized formulation of present study exhibited desired controlled drug release characteristics in the alkaline pH conditions and at acidic environment the drug dissolution was minimal as intended.

Evaluation Procedure for Quality Consistency of Generic Nifedipine Extended-Release Tablets Based on the Impurity Profile

A procedure to evaluate the quality consistency of generic drugs based on the impurity profile and the similarity analysis methods was presented in this paper. Nifedipine extended-release tablets from six generic factories of China were used to evaluate the uniformity with the original drug in the study. The procedure includes: choice of chromatographic methods, data collection and conformity test, evaluation of intra-batch similarity of drugs, evaluation of generic drugs with the original drug and weighted similarity evaluation of generic drugs. The data were collected via high-performance liquid chromatography (HPLC), and then calculated by correlation coefficient, cosine, principal component analysis (PCA) and hierarchical clustering analysis (HCA). It is more suitable to use peak areas as the vector when calculating the similarity of impurity profile. After weighting the peak areas of the unspecified impurities in further evaluation of the generic quality, the generic level of different factories was differentiated and the best generic factory was picked out.

Development of controlled release bi-layered tablets containing oxycodone hydrochloride

Oxycodone hydrochloride is a semi-synthetic opioid agonist that provides very effective relief for moderate to severe pain in cancer and post-operative patients. Controlled release oxycodone formulations have been studied to enhance the therapeutic effect by providing constant release over the whole dosing interval and improve patient’s convenience by reducing the frequency of administration as well.

Formulation development of nifedipine controlled-release coated tablets

Due to frequent administration of oral nifedipine tablet, controlled or sustained release of the drug will improve patient compliance, stable blood level and side effect decrement [1,2].Various extended release nifedipine products have been commercially available. In this study, extended release tablets of this drug were formulated using sodium alginate,hydroxypropylmethylcellulose (HPMC) as controlled release matrix materials.

Efficacy of Metoprolol Succinate Sustained Release Tablets Combined with Wenxin Granules in the Treatment of Coronary Heart Disease Arrhythmia

Objective:To explore the effect of metoprolol succinate sustained-release tablets combined with Wenxin Granules in the treatment of coronary heart disease patients with arrhythmia.Methods:The research objects were 50 patients with arrhythmia who were treated in our hospital from September 2019 to September 2020.According to different treatment methods,they were divided into observation group(Wenxin Granule+metoprolol succinate treatment)and control group(metoprolol succinate treatment),25 cases in each group.The curative effects of the two groups were compared.Results:After treatment,there was no significant difference in rnn50,RMSSD,sdnni and SDANN between the two groups(P>0.05).Compared with the control group,the SDNN in the observation group was higher than that in the control group(P<0.05);Before treatment,there was no significant difference in the above indexes between the two groups(P>0.05);The effective rates of the observation group and the control group were 92.00%and 68.00%respectively,and the curative effect of the observation group was higher than that of the control group(P<0.05);There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:In the treatment of patients with coronary heart disease and arrhythmia,Wenxin Granule Combined with metoprolol succinate sustained-release tablets has significant effect,which can effectively improve the dynamic electrocardiogram indexes of patients,improve the clinical efficacy,and has high safety.

Study the effect of formulation variables in the development of timed-release press-coated tablets by Taguchi design

In this investigation, the effect of formulation variables on the release properties of timed- release press-coated tablets was studied using the Taguchi method of experimental design. Formulations were prepared based on Taguchi orthogonal array design with different types of hydrophilic polymers (X1), varying hydrophilic polymer/ethyl cellulose ratio (X2), and addition of magnesium stearate (X3) as independent variables. The design was quantitatively evalu-ated by best fit mathematical model. The results from the statistical analysis revealed that factor X1, X3 and interaction factors between X1X2 and X1X3 were found to be significant on the re-sponse lag time (Y1), where as only factor X1 was found to be significant on the response percent drug release at 8 hrs (Y2). A numerical optimization technique by desirability function was used to optimize the response variables, each having a different target. Based on the re-sults of optimization study, HPC was identified as the most suitable hydrophilic polymer and incorporation of hydrophobic agent magnesium stearate, could significantly improve the lag time of the timed-release press-coated tablet.

Preparation and Pharmacokinetic Characterization of Sustained Release Melatonin Tablet

Aim To prepare the sustained release melatonin tablet with HPMC matrix and study its pharmacokinetics and bioavailatility. Methods HPMC was used as matrix to formulate the sustained release tablet. The influences of the size of melatonin, type and amount of HPMC, drug loading, type and amount of additives, and compressing pressure were investigated. Plasma concentration of melatonin in dogs after intravenous injection of two doses and oral administration of sustained release tablets and unmodified release capsules was detected by HPLC using fluorescence detector. Results The drug release from sustained release tablets was influenced by the size of melatonin, type and amount of HPMC, drug loading, and type and amount of additives. Melatonin was found to fit two compartment model after intravenous injection, AUC was proportional to doses, and t(1/2β) of two doses has no significant difference. Relative bioavailability of melatonin sustained release tablet to normal capsule was 83.8%, and absolute bioavailability was 3.75% for sustained release tablet and 4.49% for capsule. Conclusion The melatonin sustained release tablet was well formulated. The absolute bioavilability for oral administration of either sustained release tablet or unmodified release capsule of melatonin was less than 5%. The bioavailability of melatonin sustained release tablet was lower than that of unmodified release capsule, but MRT of sustained release tablet was significantly longer than that of capsule.

Release test of alliin/alliinase double-layer tablet by HPLC-Allicin determination

A simple, precise and accurate method was developed and validated for the determination of allicin release from alliin/alliinase double-layer tablets. According to Appendix XC Ⅱ of Chinese Pharmacopoeia 2010 edition Volume II, a small glass-method was adopted at the rotational speed of 100 r/min using 100 mL phosphate buffer （pH 6.8） as release medium. The release amount was determined by HPLC with a C18 column （250 mm × 4.6 mm, 5 μm） using the mobile phase consisting of methanol -0.4% carboxylic acid （65：35） at a flow rate of 1 mL/min and UV detection at 242 nm. The current method demonstrates good linearity over the range 4.052- 405.2 μg/mL （r2=0.9999） with an average recovery of 105.5%（RSD= 1.25%）. The accumulative release of alliin/alliinase double-layer tablets had good homogeneity for withinand betweenbatches. The method established is simple, accurate and repeatable for the determination of allicin release from alliin/alliinase double-layer tablets.

Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

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(OxyC ontin). Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroP lus 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.

Pharmacokinetic Study on Lovastatin Sustained-release Tablet and Sustained-release Capsule in Begal Dogs

This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained-release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet,T p; sustained-release capsule,T J and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. T max, C max and MRT revealed significant difference (P<0.05). Relative bioavailability was 111.5±16.9 % (T P) and 110.4%±9.6 % (T J). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, T max, C max MRT and DF had significant difference (P<0.05); C av , C min and AUC 0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.