Research progress of in vitro-in vivo correlation of injectable polylactide-polyglycolide microspheres / 药学学报

As a depot drug delivery system, injectable polylactide-polyglycolide (PLGA) sustained-release microspheres have been successfully used to treat many diseases since the first microsphere product Lupron depot was approved for marketing in the United States in 1989. It has the ability of long-term release in the body for several days to several months, which can not only reduce the times of administration, but also reduce the drug blood concentration fluctuations, significantly improve the safety and patient compliance. In vitro-in vivo correlation (IVIVC) makes the development of microspheres more possible. It can describe the dynamic information of drug release in vivo through the in vitro release behavior of microspheres, and can reduce the workload of each stage and shorten the time span while characterizing the performance of microspheres. IVIVC can provide guidance or support for drug development, production changes, supervision and management. This article summarizes the release mechanism of injectable PLGA sustained-release microspheres, common measurement methods and theories of in vitro and in vivo release. And we also focus on the establishment and application of IVIVC, especially A level IVIVC in the field of microsphere preparations, to provide a reference for further study on in vitro-in vivo correlation of microspheres.

Preparation and Formula Optimization of Diphenidol Hydrochloride Push-pull Osmotic Pump Tablets / 中国药师

Objective: To prepare diphenidol hydrochloride push-pull osmotic pump tablets and in-vestigate the influence of differ-ent factors on in-vitro drug release. Methods: The cumulative release of different formulas was detected. Using the cumulative release and similarity factor f2as the evaluation criterion, single factor experiment was applied to screen the core formula and coating process. Results: The drug release behavior was affected by the content of PEO in the drug containing layer, the content of NaCl and the weight gain of the coating layer. After the formula was optimized, the NaCl content in the drug containing layer was 10mg, the PEO-N10 con-tent was 15mg. In the push layer, the content of PEO-WSR303 was 60 mg, that of NaCl was 20 mg. The optimized coating liquid for-mula contained 1. 25 g·L-1PEG4000 and the coating weight gain was 7% of the core. The optimized formula fitted a zero-order equa-tion within 2-12h with the drug release equation of Q=6. 308t-2. 5037(r=0. 995 8). Conclusion: The preparation technology of di-phenidol hydrochloride push-pull osmotic pump tablets is stable, and the in-vitro drug release fits zero-order model.

Preparation of isoniazid delayed release implant and the release behavior in rabbits / 中国药学杂志

OBJECTIVE: To prepare isoniazid (INH) implant and evaluate the release behavior in rabbits and compare the pharmacokinetic characteristics and bioavailability of INH implant and INH tablets in rabbits.

Design and evaluation of tizanidine buccal mucoadhesive patches.

Mucoadhesive buccal dosage forms are becoming more popular and patient acceptable dosage forms. By this route advantages are many as the dose can be reduced, avoidance of first pass metabolism and liver toxicity, etc. The Tizanidine has first pass metabolism because of this the patient has to take more dose and two to three times in a day. To overcome this problem mucoadhesive patches of tizanidine are prepared and evaluated. Tizanidine is a non-selective, α-two adrenergic agonist receptor and used as muscle relaxant. The oral bioavailability of Tizanidine is 40%, because of first pass metabolism. The polymers used are polyvinyl alcohol and polyvinyl pyrolidine. FTIR and UV spectroscopic methods reveal that there is no interaction between tizanidine and polymers. The patches evaluated for various parameters and results are satisfied. In vitro release studies in phosphate buffer (pH, 6.6) exhibited drug release in the range of 71.68 to 97.27% in 90 min. The release of tizanidine from the patches followed first order, Higuchi’s model and mechanism diffusion rate limited. In vivo buccal absorption studies in rabbits showed 68.85% of drug releases from polyvinyl alcohol patch while it 67.52 to 88.31% within 90 min in human volunteers. Good correlation among in- vitro release and in- vivo studies observed.

Development and evaluation of Meloxicam solid dispersion loaded buccal patches.

Meloxicam, a non-steroidal anti-inflammatory drug is widely used in the treatment of rheumatoid arthritis, ankylosing spondulytis and osteoarthritis. It is also indicated for the management of dental pain, Post-traumatic and post-operative pain, inflammation and swelling. Recently it is considered as a potential drug for prevention and treatment of colorectal polyps. One of the major problems with this drug is its low solubility in biological fluids, which results into poor bioavailability and GI-Side effects after oral administration. The present work was aimed at overcoming these limitations of the drug. The first problem i.e. Poor solubility of meloxicam was overcome by solid dispersion technique and the same was than published in a reputed online journal. The present study was the continuation of the published work, in this study buccal patches were prepared using varying percentage of carbopol 934p, chitosan (mucoadhesive polymers) and 50% W/W of propylene glycol (Plasticizer) by solvent casting technique, using 32 factorial design. Prepared blank buccal patches were evaluated for various physical and mechanical parameters, patches which comply with reported results were selected for meloxicam and its solid dispersion incorporation. Meloxicam solid dispersion incorporated buccal patches were prepared and evaluated for drug content, in-vitro diffusion, in-vivo release of meloxicam in rabbits and stability study. All solid dispersion loaded patches showed increased in-vitro drug release (i.e. between 95% to 99.95%) over an extended period of 8hrs as compared to plain drug loaded buccal patch. Whereas plain drug loaded buccal patch showed only 31.22% in-vitro drug release in 8hrs. Meloxicam solid dispersion loaded buccal patch (MSP1) containing meloxicam solid dispersion (meloxicam 150mg, PVP250mg, PEG6000 175mg and mixture of lactose and MCC(4:1)4gm) equivalent to 7.5mg of meloxicam, 1.5% of carbopol 934p, 2% of chitosan and 50% of polymer weight of propylene glycol in each 1cm2 of the patch showed highest in-vitro drug release i.e. 99.95% in 8hrs and it followed zero order release(r=0.9961, a=8.3124, b=5.0668). The r, a and b are correlation coefficient, slope and constant respectively for the best fit kinetic model. The in-vivo release of meloxicam from its solid dispersion loaded buccal patches was also studied using rabbit model. A good in-vitro in-vivo correlation was observed in MSP1 patch. All solid dispersion loaded buccal patches showed excellent stability under tested conditions. Finally it may be concluded that buccal patches were better for improvement of release of meloxicam and also to overcome the gastric side effects of drug.

Preparation of Growth Hormone-Chitosan-Alginate Microcapsules and the Release Profile / 医学研究杂志

Objective To study the preparation and the in vitro and in vivo release profile of GH-Chitosan-Alginate microcapsules.Methods GH-Chitosan-Alginate microcapsules were prepared through impulsive electrostatic technique.The interrelated factors influencing the diameter and sphericity were studied through orthogonal experiments,and finally the statistic analysis made sure the optimum conditions to prepare microspheres.The morphology and size of the microcapsules were observed,and the content,encapsulation efficiency and recovery efficiency of the microcapsules were measured.Moreover,their in vitro and in vivo release experiments were carried out.Results The results showed that the diameter of needle was the most significant factor to the diameter of microspheres.The optimum conditions for the least diameter of microspheres were 450?m diameter of needle,2cm from needle tips to the gelation surfaee,1.5% alginate concentration,8ml/h speed of flowing-liquid and metal containers.The microcapsules had good sphericity morphology and distribution.The size of the microcapsules was in the range of 10-25?m with an average size of 47.93?m.The encapsulation efficiency and GH-load of the microcapsules were 94% and 11.24% respectively.The release kinetics of microcapsules was studied in false gastric and intestines juice.In false gastric juice,the GH of microcapsules was not released;in false intestines juice,it was released well,and TAM was completely released after about 12h.in vivo release profile made sure that the serum GH level of GH microcapsule group was at the highest value(98.59ng/ml) at 8h.The release profile was fitted well in both in vitro and in vivo conditions.Conclusion GH-Chitosan-Alginate Microcapsules have good morphology and sustained release effect.

Bioequivalence of Progesterone Sustained Release Suppository in Rabbits / 华中科技大学学报（医学）（英德文版）

To study the bioequivalence of a kind of progesterone sustained release suppository, a randomized cross-over study was conducted in 12 rabbits. A single rectal dose of 2.75 mg/kg progesterone sustained released suppository (tested formulation, T) and progesterone suppository(reference formulation, R) was administered; a multiple dose of 2.75 mg/kg was given up to seven times with an interval of 8 h. Concentrations in serum were determined by a competitive enzyme immunoassay. The main parameters of T were: for single and multiple doses, Cmax was 48.8±11.8ng/mL and 43.5±9.4 ng/mL, Tmax was 0.5±0.3 h and 0.4±0.3 h, AUC(0-24h) was 362.4±143 ng·h·mL-1 and 310.6±70.3ng ·h·mL-1,respectively.The relative bioavailability of T to R were ( 104.2 ±13.4) % and ( 111.4 ± 19. 1 ) %, respectively. Statistical analysis showed that the two formulations were bioequivalent and T had sustained released feature.