Preparation and in vitro release profiling of PLGA microspheres containing BSA as a model protein

Conventional drug formulations are incapable of adequate delivery of proteins and peptides for therapeutic purposes. As these molecules have very short biological half-life, multiple dosing is required to achieve the desirable therapeutic effects. Microspheres are able to encapsulate proteins and peptide in the polymeric matrix while protecting them from enzymatic degradation. In this study Bovine Serum Albumin (BSA) matrix type microspheres were fabricated using Polylactide-co-glycolide (PLGA) by double emulsion solvent evaporation method. The effects of variables such as homogenizer speed, molecular weight of polymer and the effect of pH of the water phases, were investigated against factors such as drug loading, encapsulation efficiency, morphology, size, drug distribution and release profile of the microspheres. Results, suggested that an increase in homogenization speed leads to a decrease in microsphere size. The increase in homogenization speed also caused a significant effect on the release profile only when higher molecular weight of polymer had been used.. The pH change of the internal aqueous phase led to modification of surface morphology of spheres to a porous structure that significantly increased the total amount of released protein. Integrity of protein structure was intact as shown by SDS-PAGE. According to the results, it can be concluded that we achieved a reproducible method regarding controlled protein delivery for different sizes of particles.

In vitro-in vivo correlation of goserelin acetate microspheres / 药学学报

The objective of this paper was to establish a level A in vitro-in vivo correlation (IVIVC) for goserelin acetate extended release microspheres for injection. Three kinds of goserelin acetate microspheres with different release rates were prepared and the critical physicochemical properties, such as drug loading, particle size, glass transition temperature and morphology were characterized. In vitro dissolution test of the prepared goserelin acetate microspheres was performed using sample-and-separate method at 45 ℃ in 5% (v/v) methanol. The morphology of the microspheres and the molecular weight of poly (lactic-co-glycolic acid) (PLGA) of the prepared goserelin acetate microspheres were investigated to research the release mechanism of microspheres. The plasma concentration of goserelin was detected after intramuscular injection of goserelin acetate microspheres to SD rats, and correlated with the in vitro release profiles after processing by percent AUC method. The pharmacokinetic experimental protocol of goserelin acetate microspheres for injection in SD rats was approved by the Animal Ethics Committee of Shandong Luye Pharmaceutical Co., Ltd. The results indicated that the developed sample and separate method was able to detect differences in the release characteristics of the prepared goserelin acetate microspheres, and the in vitro-in vivo correlation of goserelin acetate microspheres was excellent (r > 0.98) and had good predictive ability in SD rats.

Physicochemical, biological and release studies of chitosan membranes incorporated with Euphorbia umbellata fraction

Abstract Formulations containing chitosan incorporated with methanolic fraction of Euphorbia umbellata (Pax) Bruyns, Euphorbiaceae, were studied aiming future applications of this new material as medicine. In order to investigate potential interactions between chitosan and the methanolic fraction (10, 50 and 100% in relation to the amount of chitosan) physicochemical characterization was performed by scanning electron microscopy, density, differential scanning calorimetry, thermogravimetry, X-ray diffraction, Fourier-transform infrared spectroscopy and colorimetry techniques. The phenolic compounds released from the chitosan membranes were evaluated using the Folin-Ciocalteau quantification method; antioxidant and antimicrobial activity were also studied. Increasing amounts of the methanolic fraction added to polymeric matrix produced different numbers of pores on the surface of the membranes, changes in the calorimetric, spectroscopic and crystalline properties as well as color changes, when compared to the inert membrane. These changes can be attributed to chemical interactions that occurred between the structure of the chitosan and the phenolic compounds present in the studied fraction. The matrix samples incorporated with 50 and 100% of the methanolic fraction presented different release profiles of phenolic compounds from the membranes (controlled manner) and promoted antioxidant and antimicrobial activity.

Formulation of gastroresistant tablets containing sodium alendronate-loaded blend microparticles / Formulação de comprimidos gastro-resistentes que contêm na mistura micropartículas carregadas de alendronato de sódio

Sodium alendronate is an antiresorptive drug used for the treatment of postmenopausal osteoporosis. However, its oral administration is associated with low bioavailability and gastroesophageal irritation. This work aimed at developing tablets containing sodium alendronate-loaded microparticles by direct compression to achieve a safe and effective form. The parameters evaluated were average weight, hardness, thickness and drug content. In vitro release tests were carried out using simulated gastric and intestinal fluids, and the profiles were analyzed through the Korsmeyer-Peppas mono- or biexponential dependent approaches. Tablets presented adequate average weight, thickness, good mechanical properties and drug content close to 100%. Moreover, the formulation released less than 11% of sodium alendronate in gastric fluid, exhibiting a good gastroresistance. At pH 6.8, almost 100% of the drug was released in 12h, showing a prolonged profile. The mathematical modeling indicated that the experimental data was better fitted to the biexponential equation. Furthermore, a good correlation coefficient was obtained for the Korsmeyer-Peppas model and the release exponent suggested that the drug dissolution was driven by anomalous transport. In conclusion, the microparticulated tablets can be considered a promising alternative for oral delivery of sodium alendronate...

O alendronato de sódio é um fármaco da classe dos bisfosfonatos, comumente utilizado no tratamento da osteoporose pós-menopausa. Entretanto, sua administração oral está associada à baixa biodisponibilidade e irritação gastroesofágica. Este trabalho objetivou o desenvolvimento de comprimidos contendo micropartículas de alendronato de sódio por compressão direta, a fim de obter uma forma segura e eficaz. Os parâmetros avaliados foram peso médio, dureza, espessura e teor de fármaco. Estudos de liberação in vitro foram realizados utilizando fluído gástrico e intestinal simulado e o perfil de liberação foi analisado pelos modelos matemáticos de Korsmeyer-Peppas, mono- e biexponencial. Os comprimidos apresentaram peso médio adequado, espessura, dureza e teor próximo a 100%. Além disso, a formulação liberou menos de 11% do fármaco em fluído gástrico, mostrando uma boa gastrorresistência. Em pH 6,8, em torno de 100% do fármaco foram liberados em 12 h, apresentando liberação prolongada. A modelagem matemática indica que os resultados seguem a equação biexponencial. Pela análise do expoente de liberação obtido no modelo de Korsmeyer-Peppas sugere-se que a dissolução do fármaco ocorre por transporte anômalo. Concluindo, a preparação dos comprimidos microparticulados pode ser considerada uma alternativa promissora para a liberação oral do alendronato de sódio...

Preparation and performance of LID-MWCNT based sustained release targeted drug delivery system / 天津医药

Objective To prepare a targeted antitumor drug delivery system using large-inner-diameter multi-walled carbon nanotubes (LID-MWCNTs) for sustained release and to study its performance. Methods LID-MWCNTs were puri?fied and oxidized,then use nanocarriers and USTs as homologous blockers. Folic acid and fluorescent labels were conjugat?ed onto the external surfaces of nanocarriers. CDDP (cisplatin) was encapsulated and ultrashort tubes (USTs) were employed to block the drug entry/exit paths. The microstructure of resulted drug delivery system (DDS) was observed, while drug load?ing efficiency and drug release profile in vitro were determined. The tumor-targeting property and cytotoxicity of DDS were also assessed. Results LID-MWCNT based sustained release targeted drug delivery system was established. Drug loading efficiency of CDDP@UST-FA-LID-MWCNTs was as high as 70.97%. A typical biphasic sustained release pattern was dem?onstrated, and the accumulating release time was 18 h. DDS exhibited a certain kind of tumor-targeting property, and inhibit?ed proliferation of tumor cells in a dose-dependent manner. Conclusion CDDP@UST-FA-LID-MWCNT drug delivery system exhibited an improved drug loading efficiency and a sustained drug release profile. It could specifically target the tu?mor cells and had a significant antitumor effect.

Formulation and in vitro evaluation of mucoadhesive controlled release matrix tablets of flurbiprofen using response surface methodology

The objective of the current study was to formulate mucoadhesive controlled release matrix tablets of flurbiprofen and to optimize its drug release profile and bioadhesion using response surface methodology. Tablets were prepared via a direct compression technique and evaluated for in vitro dissolution parameters and bioadhesive strength. A central composite design for two factors at five levels each was employed for the study. Carbopol 934 and sodium carboxymethylcellulose were taken as independent variables. Fourier transform infrared (FTIR) spectroscopy studies were performed to observe the stability of the drug during direct compression and to check for a drug-polymer interaction. Various kinetic models were applied to evaluate drug release from the polymers. Contour and response surface plots were also drawn to portray the relationship between the independent and response variables. Mucoadhesive tablets of flurbiprofen exhibited non-Fickian drug release kinetics extending towards zero-order, with some formulations (F3, F8, and F9) reaching super case II transport, as the value of the release rate exponent (n) varied between 0.584 and 1.104. Polynomial mathematical models, generated for various response variables, were found to be statistically significant (P<0.05). The study also helped to find the drug's optimum formulation with excellent bioadhesive strength. Suitable combinations of two polymers provided adequate release profile, while carbopol 934 produced more bioadhesion.

O objetivo do presente estudo foi formular comprimidos mucoadesivos de flurbiprofeno, de liberação controlada, e otimizar o perfil da liberação do fármaco e a bioadesão, utilizando a metodologia de superfície de resposta. Prepararam-se os comprimidos via técnica de compressão direta, que foram avaliados in vitro quanto aos parâmetros de dissolução e da força bioadesiva. Planejamento com componente central para dois fatores em cinco níveis cada foi empregado para esse estudo. Carbopol 934 e carboximetilcelulose sódica foram tomados como variáveis independentes. Efetuaram-se estudos de espectroscopia por transformada de Fourier (FTIR) para observar a estabilidade do fármaco durante a compressão direta e para avaliar a interação a fármaco-polímero. Aplicaram-se vários métodos cinéticos para avaliar a liberação do fármaco dos polímeros. Gráficos de superfície de contorno e de resposta foram efetuados para retratar a relação entre as variáveis dependentes e a resposta. Os comprimidos mucoadesivos de flurbiprofeno apresentaram cinética de liberação não-fickiana, estendendo para ordem zero, para algumas formulações (F3, F8 e F9), alcançando transporte super caso II, à medida que o valor do expoente (n) de taxa de liberação variou entre 0,584 e 1,104. Modelos matemáticos polinomiais, gerados por diversas variáveis de resposta, foram estatisticamente, significativos (P<0,05). O estudo também auxiliou a encontrar a formulação ótima do fármaco, com excelente força de bioadesão. Combinações adequadas dos dois polímeros resultaram em perfis de liberação adequado, sendo que o Carbopol 934 produziu mais adesão.

Effect of superdisintegrants and their mode of incorporation on disintegration time and release profile of carbamazepine from immediate release tablet.

In this experiment the effect of mode of incorporation of some superdisintegrants such as sodium starch glycolate, croscarmellose sodium, crospovidone (kollidon CL), ludiflash and Xanthan gum (XG) on dissolution profile and disintegration time of carbamazepine (CBZ), apoorly water soluble drug was studied. The superdisintegrants were incorporated by extragranularly, intragranularly and in direct compression method. Different amount of superdisintegrants (1%, 3% and 6%) was incorporated in different formulations whereas all the other excipients as well as the active drug remained same. The results indicated that sodium starch glycolate, when incorporated extragranularly in wet granulation method significantly enhanced the release profile of CBZ. Kollidon CL was the most effective superdisintegrant in decreasing disintegration time of different tablet formulations (1.95 minutes when extragranularly incorporated). On the other hand, tablets prepared with SSG were found most effective in % drug release irrespective of its mode of incorporation (99.99% when extragranularly incorporated and 99.75 when intragranularly incorporated within one hour). Tablets prepared by direct compression method also showed similar drug release with other methods but tablet hardness was found lower. So addition of superdisintegrants in tablet formulation may be an effective technique to comply compendial drug release.

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.

Preparation of Triptolide-loaded Microspheres and Its Release Profile in Vitro and in Vivo / 中国药房

OBJECTIVE:To prepare triptolide-loaded sustained release microspheres and investigate its release profile in vivo and in vitro.METHODS:Triptolide-loaded sustained release microspheres were prepared by solvent evaporation method.A motionless method was used to investigate the process of release in vitro.The in vivo release process was investigated by pharmacokinetic experiment in rats.RESULTS:The microspheres were round and smooth examined by optical microscope.The size of triptolide loaded microspheres was(38.2?1.7) ?m and the encapsulation efficiency of triptolide loaded microspheres was(74.7?3.2)%.A constant in vitro release of triptolide-loaded microspheres was noted.The pharmacokinetic parameters of microspheres in vivo were as follows:Cmax was(114.7?31.90) ng?mL-1;tmax was(8.32?4.43) h;AUC was(1 774 282?1 046 152) ng?h?mL-1 and MRT was(596?165) h.In addition,the in vivo-in vitro correlation was good,r=0.955 3(P