Preparation and evaluation of sirolimus sustained release tablets based on mesoporous silicon loaded self-microemulsion / 药学学报

Sirolimus self-microemulsion-mesoporous silicon sustained release tablets were prepared in order to improve the dissolution of the insoluble drug sirolimus and reduce its side effects. Firstly, sirolimus self-microemulsion was prepared and cured with mesoporous silicon. Secondly, the suitable excipients were selected according to the appearance, hardness and in vitro release rate. The sustained-release tablets with hydroxypropyl methylcellulose (HPMC) as skeleton material were prepared by powder direct pressing method, and the formulation was optimized by central composite design-response surface method to investigate the drug release in vitro. Finally, the pharmacokinetics was carried out in beagle dogs using the commercial sirolimus tablets as references. The final formulation of sustained-release tablets is as follows: 162 mg of sirolimus self-microemulsion-mesoporous silica (1∶1, w/w), 80 mg of HPMC K4M and 80 mg of carboxymethyl starch sodium, the microcrystalline cellulose is 168 mg. The results of in vitro release test showed that the self-made sustained-release tablets released slowly within 12 h, which conformed to the Ritger-Peppas model. The in vivo test results showed that compared with the commercial sirolimus tablets, the Cmax of the sustained-release tablets decreased by 49.47%, the Tmax of the sustained-release tablets was prolonged by 5.1 times, and the relative bioavailability was 105.81%. Sirolimus self-microemulsion-mesoporous silicon sustained-release tablets have good sustained-release effects in vitro and in vivo, which provides a reference for the solubilization of other insoluble drugs and the research and development of sustained-release preparations. Animal experiments and welfare processes were reviewed and approved by the Animal Ethics Committee of the 900TH Hospital of the Joint Logistics support Force.

Characterization of the critical quality attributes for hydroxypropyl methylcellulose with different sources and analysis of the release of sustained-release tablets in vitro / 药学学报

The quality difference of pharmaceutical excipients from different sources affects the molding properties of the powder, resulting in changes in the properties of the final product. In this study, the critical quality attributes of hydroxypropyl methylcellulose (HPMC) with different specifications from two manufacturers (manufacturer A and manufacturer B) were characterized including particle size, physical morphology, viscosity and powder physical quality attributes. Aminophylline, diclofenac sodium, and metformin hydrochloride were utilized as model drugs with different solubility to prepare sustained-release tablets, and the effect of HPMC from different sources on drug release of sustained-release tablets in vitro was investigated. The results showed that HPMC with the same viscosity specification from different sources had outstanding differences in the physicochemical properties (including particle size, physical morphology, viscosity, dimension, compressibility and powder flow), which could change the hardness and friability of the sustained-release tablets. The differences in the physicochemical properties of HPMC had different effects on the dissolution of different sustained-release tablets in vitro. It had no significant effect on the release of easily soluble aminophylline and metformin hydrochloride, but had a greater impact on the release of poorly soluble diclofenac sodium. Compared with manufacturer A, the sustained-release effect of matrix tablets prepared by HPMC from manufacturer B was more excellent. The results of this study will provide a theoretical reference on selecting the appropriate excipients for formulation design.

Characterization and principal component analysis of functionality-related characteristics of hydroxypropyl methylcellulose type 2208 / 药学学报

Under the guidance of Chinese Pharmacopoeia (2020 edition), the functionality-related characteristics of hydroxypropyl methylcellulose (HPMC) type 2208 from imported A manufacturer, domestic S manufacturer, domestic T manufacturer and different batches of the same manufacturer were characterized. The principal component analysis was used to comprehensively evaluate the functionality-related characteristics. The results were as follows: hydroxypropyl methylcellulose had no significant difference in viscosity and molecular weight distribution between different manufacturers, and there were significant differences in the cumulative particle size distribution of the sample reaches 50% (d50) and 90% (d90), bulk density, tap density and Carr's index. The HPMC from A manufacturer have the biggest inter-batch difference of particle size and their inter-batch difference of polydispersion coefficientis smaller than S manufacturer. Domestic manufactures have the largest inter-batch difference in other functionality-related characteristics. The three principal components were extracted by principal component analysis, and the variance contribution rate reached 89.44%, indicating that the extracted principal components can explain all the data well. By constructing a comprehensive evaluation model, the comprehensive score ranking of all HPMC samples is obtained: S manufacturer > A manufacturer > T manufacturer.

Preparation And Characterization Of Hydroxypropyl Methylcellulose Produced From Α-Cellulose Betung Bamboo (DENDROCALAMUS Asper) And It’s Evaluation On Gel Formulation

Objective: This study aim to obtain the optimum condition of preparation of hydroxypropyl methylcellulose (HPMC) produced from α-cellulose betung bamboo, physicochemical properties of HPMC powder and its characteristics in a gel formulation. Methods: HPMC of betung bamboo (HPMC BB) were optimized by central composite design (CCD) using three variables (sodium hydroxide concentration, dimethyl sulfate concentration, and temperature) and five levels (0,±1, and±α). The suggested optimum condition was subjected to further characterization. HPMC BB was characterized using Fourier transform infrared (FTIR) spectrometry, particle size analyzer (PSA), x-ray diffraction (XRD), scanning electron microscope (SEM) and compared to HPMC 60SH as the reference. Then, HPMC BB was used as a gelling agent in a gel formulation and the gel was evaluated, including appearance and homogeneity, pH, viscosity, and spreadability. Results: Optimum condition of preparation of HPMC BB was using sodium hydroxide 27.68% (w/v) and 1.26 ml dimethyl sulfate (based on 1 g α-cellulose) at 58.11 °C which resulted in molar substitution 0.21 and degree of substitution 2.09. The results showed that HPMC BB was a fine powder with yellowish-white color, odorless and tasteless, pH 7.02, residue on ignition 1.39%, methoxy groups content 28.56%, hydroxypropoxy groups content 7.09%, mean particle size 98.595 μm, loss on drying 3.62%, and moisture content 7.47%. Flow properties of HPMC BB classified in the fair category. The infrared spectrum and diffraction patterns were relatively similar to HPMC 60SH. The gel has a good homogeneity and spreadability and viscosity 142.5 mPa⋅s. pH 6.37. Conclusion: Based on the comparison to reference, HPMC BB showed relatively similar physicochemical and powder properties. However, HPMC BB is not recommended as a gelling agent in gel formulation because it has a low viscosity.

Floating ability and drug release evaluation of gastroretentive microparticles system containing metronidazole obtained by spray drying

Abstract Gastroretentive floating microparticles were developed and evaluated for the controlled metronidazole delivery for treatment of gastric disease. Floating microparticles, varying in proportions of chitosan and hydroxypropyl methylcellulose or ethylcellulose, were obtained by spray drying. Floating microparticles were characterized by physicochemical and in vitro studies, according to their floating ability and drug delivery. Microparticles presented mean diameter from 1.05 to 2.20 µm. The infrared spectroscopy confirmed the drug encapsulation and showed no chemical linkage between microparticles components. X-ray diffraction showed changes in the drug`s solid state, from crystalline to amorphous, indicating partial drug encapsulation, due to the presence of some crystalline peaks of metronidazole in microparticles. All microparticles floated immediately in contact of simulated gastric fluid and both floating and drug release profiles were dependent of microparticles composition. Microparticles samples constituted by chitosan and hydroxypropyl methylcellulose revealed the best relationship between floating duration and drug release, remaining floating during the occurrence of the drug release, ideal condition for the floating gastroretentive systems.

In vitro evaluation of sustained released matrix tablets containing ibuprofen: a model poorly water-soluble drug

ABSTRACT A matrix system was developed that releases ibuprofen (IB) over a 12-hour period and the influence of the polymer type and concentration on the release rate of the drug was evaluated. Tablets containing different concentrations of Carbopol (CP), hydroxypropyl methylcellulose (HPMC), or ethyl cellulose (EC) were prepared using direct compression and the drug content, content uniformity, hardness, friability, dissolution performance, and in vitro release kinetics were examined. Formulated tablets were found to be within acceptable limits for physical and chemical parameters. The release kinetics of the Carbopol(r)971P 8% formulation showed the best linearity (r 2 =0.977) in fitting zero-order kinetics, suggesting the release rate was time independent. The drug release from tablets containing 8% CP was extended over approximately 18 hours and the release kinetics were nearly linear, suggesting that this system has the potential to maintain constant plasma drug concentrations over 12 hours, which could reduce the frequency of administration and the occurrence of adverse effects associated with repeated administration of conventional IB tablets.

The swelling behavior of choline fenofibrate hydrogel matrix tablets using dynamic image analysis / 药学学报

The purpose of this study is to investigate the effects of formulation on the swelling behavior of choline fenofibrate hydrogel matrix tablets and reveal the relation between swelling property and release profile using dynamic image analysis. The volume swelling ratio (SR) and height/width (k) could evaluate the swelling behavior of matrix tablets well. The mount of hydroxypropyl methylcellulose (HPMC) and the ratio between K15M and K4M affected the volume swelling ratio, while PVP didn't. The three factors all impacted k, which was an indicator of the strength of the gel formed by HPMC. The accumulative release ratio and SR, the rate of swelling and the rate of release were compared. The proper model equations were established for the results with an excellent correlation. The results prove that there is a strong relevance between the swelling behavior and release property. This study provides a guideline in the study design for hydrogel matrix tablets.

Aplicación y efecto de un recubrimiento comestible sobre la vida útil de la mora de castilla (Rubus glaucus Benth) / Edible coating application and effect on blackberry (Rubus glaucus Benth) shelf life

Antecedentes: En los últimos años ha incrementado el interés por el consumo de frutas en estado fresco debido al potencial nutricional que estas contienen. Además, por el alto consumo energético que se generan en la aplicación de una cadena en frío, se ha incursionado en la aplicación de recubrimientos comestibles como una técnica alternativa para la conservación de frutas. Objetivos: Por tal razón, este trabajo tuvo como objetivo aplicar un recubrimiento a base de hidroxipropil metilcelulosa con la inclusión de cera de abejas en mora de castilla y evaluar su efecto en la conservación de esta fruta. Métodos: Se trabajó con un diseño multifactorial categórico y el análisis estadístico utilizado fue el LSD de Fisher con un nivel de confianza del 95%; determinándose propiedades fisiológicas tales como respiración y pérdida de peso, propiedades fisicoquímicas como pH, acidez titulable, sólidos solubles totales e índice de maduración durante un periodo de 15 días a una temperatura de 4°C. Resultados: Se obtuvo diferencias significativas (p < 0,05) entre los tratamientos evaluados a partir del tercer día de almacenamiento tanto para los parámetros fisicoquímicos como fisiológicos. La acidez titulable tuvo un decrecimiento marcado en el tratamiento control (T5) con respecto a los tratamientos donde se aplicó los recubrimientos (T1, T2, T3, T4) donde el descenso de la acidez fue menor. Por otro lado, la pérdida de peso, los sólidos solubles totales, el pH, el índice de maduración y el índice de respiración incrementaron a medida que el tiempo de almacenamiento transcurrió, indicando que las moras tratadas con los recubrimientos tuvieron un incremento menor con respecto a las moras sin recubrimiento. Conclusiones: Los recubrimientos comestibles aplicados a la mora de castilla tuvieron un efecto positivo sobre las propiedades evaluadas, siendo los mejores tratamientos el T3 y T4. En general, la aplicación de un recubrimiento comestible a base de hidroxipropil metilcelulosa y cera de abejas logró aumentar la vida útil de la mora de castilla.

Background: On the last years the interest on fresh fruits consumption has been increased due to its nutritional potential as well as high energetic demand generated by the cold-chains storage. It is the reason why it has been dabbled on edible coating as an alternative method on fruits preservation. Objectives: This investigation focused on the coating application using a hydroxypropyl methylcellulose based with bees wax applied all over blackberry fruits in order to evaluate the effects on its preservation. Methods: A multifactorial categorical design was used through the Fisher LSD method as an statistical analysis with a confidence level of 95%; it were determined physiological properties such respiration and weight loss, and physicochemical properties like pH, titratable acidity, soluble solids, and ripeness index within a period of 15 days at 4°C. Results: It were obtained significant differences (p<0.05) between the evaluated treatments from the third storage day for physicochemical and physiological parameters. The titratable acidity has a marked decrease on the control treatment (T5) regarding treatments where coatings were applied (T1, T2, T3, T4) where a smaller decrease on acidity was obtained. In other hand, the weight loss, total soluble solids, pH, ripening and respiration index showed an increase over storage time. The blackberry fruits processed with edible coating presented a slight increase compared to control samples. Conclusions: Edible coatings applied on blackberry fruits had a positive effect in the evaluated properties, treatments T3 and T4. Generally, edible coatings with hydroxypropyl methylcellulose base and beeswax increase the shelf life of blackberry.

Preparation and Release Characteristics of Venlafaxine Hydrochloride Hydrophilic and Lipidic Matrix Sus-tained-release Tablets / 中国药房

OBJECTIVE:To prepare Venlafaxine hydrochloride sustained-release tablets,and to investigate the characteristics of drug release. METHODS:Using glyceryl behenate as lipidic matrix material and HPMC as hydrophilic matrix material,the kind and dosage of excipients were screened by single factor experiment. Using 4,8,24 h accumulative release rate and the deviation summation of ideal values as index,the viscosity of HPMC,the amounts of HPMC K15M and glyceryl behenate were optimized by orthogonal test. The dissolution curves were fitted by different equations. RESULTS:The optimal formulation was as follows as venlafaxine hydrochloride 8.5 kg,HPMC K15M 15 kg,glyceryl behenate 26 kg,magnesium stearate 0.5 kg. 4,8,24 h accumula-tive release rates of prepared matrix sustained-release tablets were 34.3%,63.9% and 99.2%,respectively. The releases profiles of hydrophilic and lipidic matrix sustained release tablets followed first-order equation in vitro mainly through matrix erosion. CON-CLUSIONS:Venlafaxine hydrochloride hydrophilic and lipidic matrix sustained-release tablets with good sustained-release effect have been prepared successfully.

Effects of Hydrophilic Polymers on the Stability of Self-microemulsifying Drug Delivery Systems / 中国药房

OBJECTIVE:To investigate the effects of hydrophilic polymers on the stability of self-microemulsifying drug deliv-ery systems (SMEDDS). METHODS:Taking felodipine (FDP) as model drug,the content of FDP was determined by HPLC method. The effects of pure water,0.5% Kollidon VA64,HPMC E5,HPMC K100LV,HPMC K4M,PVP K30 solution,while 0.1%,0.5% and 1.0% HPMC E5 and Kollidon VA64 on residual content of dissolved FDP were determined in SMEDDS. RE-SULTS:The residual contents of dissolved FDP in SMEDDS placed in Kollidon VA64,HPMC E5,HPMC K100LV,PVP K30, HPMC K4M and pure water for 1 h were 92.7%,63.6%,50.2%,46.2%,36.0%and 24.0%,respectively. The order of maintain-ing the supersaturation state was Kollidon VA64>HPMC E5>HPMC K100LV>PVP K30>HPMC K4M>pure water. The residu-al contents of dissolved FDP in SMEDDS placed in 0.1%,0.5%,1% Kollidon VA64 and HPMC E5 and pure water for 1 h were 93.2%,95.1%,96.0% and 48.4%,62.1%,75.1%. CONCLUSIONS:Kollidon VA64 and HPMC E5 can significantly inhibit drug release in SMEDDS and be used as stabilizer of SMEDDS,wherein Kollidon VA64 was better.

Formulation and Characterization of Ketoprofen Emulgels.

The present study was intended to formulate the ketoprofen emulgels using different viscosity grades of hydroxypropyl methylcellulose and carbopol as gelling agents. All the prepared emulgels were shown acceptable physical properties concerning colour, homogeneity, consistency, and pH value. Emulgels containing hydroxypropyl methylcellulose were poor in clarity when compared to carbopol formulations. The influence of the type of gelling agent on the drug release from the prepared emulgels was investigated and carbopol 934 showed good results not only in the drug release but also in physical evaluation parameters. From the drug release studies, F3 formulation showed 98.46±2.05% drug release in 8 h with good clarity and physical appearance. The T10% and T80% values of best formulation F3 was found to be 0.9 h and 6.6 h respectively. The T10% and T80% was higher for formulations with carbopol in low concentration when compared to hydroxypropyl methylcellulose K 4M and K 15M in high concentrations, indicating better controlled release. FTIR studies proved the compatibility between drug and carbopol. From the stability studies, similarity index value between dissolution profiles of F3 formulation before and after storage was found to be 87.16. Hence the development of ketoprofen emulgels is a suitable way for topical administration.

Preparation and characterization of ginsenoside Rg3 solid dispersion / 中国药学杂志

OBJECTIVE: To prepare ginsenoside Rg3 (G-Rg3) solid dispersion by atoping a new technology to increase the solubility of G-Rg3. METHODS: Hydroxypropyl methylcellulose acetate succinate (HPMCAS) was selected as the carrier to prepare G-Rg3 solid dispersion. The G-Rg3 solid dispersion was characterized via Fourier transform infrared spectroscopy, X-ray diffractometry, differential scanning calorimetry analysis, and scanning electron microscopy. The equilibrium solubility of G-Rg3 and G-Rg3 solid dispersion were measured by using high-performance liquid chromatography. RESULTS: The G-Rg3 solid dispersion was successfully prepared. The solubility of G-Rg3 solid dispersion in the weak acid medium (pH 5.5 and 6.4) designed to simulate human duodenum and jejunum was significantly higher than that of G-Rg3. CONCLUSION: The preparation method of G-Rg3 solid dispersion is simple, economic, and practical, which can obviously increase the of solubility of G-Rg3.

Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets

The aim of the present study was to develop tizanidine controlled release matrix. Formulations were designed using central composite method with the help of design expert version 7.0 software. Avicel pH 101 in the range of 14-50% was used as a filler, while HPMC K4M and K100M in the range of 25-55%, Ethylcellulose 10 ST and 10FP in the range of 15 - 45% and Kollidon SR in the range of 25-60% were used as controlled release agents in designing different formulations. Various physical parameters including powder flow for blends and weight variation, thickness, hardness, friability, disintegration time and in-vitro release were tested for tablets. Assay of tablets were also performed as specified in USP 35 NF 32. Physical parameters of both powder blend and compressed tablets such as compressibility index, angle of repose, weight variation, thickness, hardness, friability, disintegration time and assay were evaluated and found to be satisfactory for formulations K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 & KSR9. In vitro dissolution study was conducted in 900 ml of 0.1N HCl, phosphate buffer pH 4.5 and 6.8 medium using USP Apparatus II. In vitro release profiles indicated that formulations prepared with Ethocel 10 standard were unable to control the release of drug while formulations K4M2, K100M9, E10FP2 & KSR2 having polymer content ranging from 40-55% showed a controlled drug release pattern in the above mentioned medium. Zero-order drug release kinetics was observed for formulations K4M2, K100M9, E10FP2 & KSR2. Similarity test (f 2) results for K4M2, E10FP2 & KSR2 were found to be comparable with reference formulation K100M9. Response Surface plots were also prepared for evaluating the effect of independent variable on the responses. Stability study was performed as per ICH guidelines and the calculated shelf life was 24-30 months for formulation K4M2, K100M9 and E10FP2.

O objetivo do presente estudo foi desenvolver matriz de de tizanidina de liberação controlada. As formulações foram projetadas usando o método do componente, central com a ajuda de software Design expert(r), versão 7.0. Utilizou-se Avicel pH 101, no intervalo de 14-50%, como material de preenchimento, enquanto HPMC K4M e K100M, no intervalo de 25-55%, Etilcelulose 10 ST e 10FP, no intervalo de 15-45% e Kollidon SR, na faixa de 25-60% foram utilizados como agentes de liberação controlada, no planejamento de formulações diferentes. Vários parâmetros físicos, incluindo o fluxo de pó para as misturas e variação de peso, espessura, dureza, friabilidade, tempo de desintegração e liberação in vitro, foram testados para comprimidos. Ensaios dos comprimidos foram, também, realizados, tal como especificado em USP 35 NF 32. Avaliaram-se os parâmetros físicos de ambos, mistura em pó e comprimidos, como índice de compressibilidade, ângulo de repouso, variação de peso, espessura, dureza, friabilidade, tempo de desintegração e de ensaio, considerando-os satisfatórios para as formulações K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 e KSR9. O estudo de dissolução in vitro foi realizado em 900 mL de HCl 0,1 N, tampão de fosfato pH 4,5 e meio 6,8, usando aparelho USP II. Os perfis de liberação in vitro indicaram que as formulações preparadas com Ethocel 10 padrão não foram capazes de controlar a liberação do fármaco, enquanto as formulações K4M2, K100M9, E10FP2e KSR2, com teor de polímero variando entre 40 e 55% apresentaram padrão de liberação controlada de fármaco no meio anteriormente mencionado. Observou-se cinética de liberação de fármaco de ordem zero para as formulações K4M2 , K100M9, E10FP2 e KSR2. Resultados do teste de similaridade (f 2) para K4M2, E10FP2 e KSR2 foram comparáveis com a formulação de referência K100M9. Gráficos de superfície de resposta também avaliaram o efeito da variável independente sobre as respostas. Estudo de estabilidade foi realizado conforme as diretrizes do ICH e a vida de prateleira calculada foi de 24-30 meses para as formulações K4M2, K100M9 e E10FP2.

Characterization and evaluation of the release kinetics of a model poorly water-soluble and low dose drug from matrix tablets composed of blends of swellable and erodible polymers: implications for controlled and complete release.

The specific aim of this study was to prepare sustained release matrix tablets containing indapamide as a low dose and low water solubility model drug. The matrix formers were composed of blends of hydroxypropyl methylcellulose as a swellable polymer and methyl cellulose as an erodible polymer. The matrix tablets were prepared by the direct compression technique and they have shown robust and acceptable physical properties with a content uniformity within the acceptable limits. Lactose and microcrystalline cellulose were investigated as additives to these matrices in order to adjust and modulate the release of the drug from the matrices to achieve a release profile similar to that obtained from the reference commercial product, Natrilix®. All matrix tablets prepared with these two additives have gave a release profile that is close to zero order kinetics, however, the matrix tablets prepared with lactose gave a release profile with closer resemblance to that of the reference product with a similarity factor (F2) of 86. This is attributed to the rapid water solubility of lactose which enhanced higher erosion of the tablets, and thus, higher dissolution and diffusion of the drug. Microcrystalline cellulose is a swellable polymer where it has resulted in delayed release of the drug with time as compared to the reference product. Investigation of the mechanism of release of the drug from the matrices indicated that erosion is the dominant mechanism of drug release from these matrices.

Alginate/hydrophobic HPMC (60M) particulate systems: new matrix for site-specific and controlled drug delivery

This study aimed to obtain site-specific and controlled drug release particulate systems. Some particulates were prepared using different concentrations of sodium alginate (Na-Alg) alone and others were formulated using different proportions of Na-Alg with hydroxypropyl methylcellulose (HPMC) stearoxy ether (60M viscosity grade), a hydrophobic form of conventional HPMC, using diclofenac potassium (DP) by ion-exchange methods. Beads were characterized by encapsulation efficiency, release profile, swelling, and erosion rate. The suitability of common empirical (zero-order, first-order and Higuchi) and semi-empirical (Ritger-Peppas and Peppas-Sahlin) models was studied to describe the drug release profile. The Weibull model was also studied. Models were tested by non-linear least-square curve fitting. A general purpose mathematical software (MATLAB) was used as an analysis tool. In addition, instead of the widely used linear fitting of log-transformed data, direct fitting was used to avoid any sort of truncation or transformation errors. The release kinetics of the beads indicated a purely relaxation-controlled delivery, referred to as case II transport. Weibull distribution showed a close fit. The release of DP from Na-Alg particulates was complete in 5-6 hours, whereas from Na-Alg hydrophobic HPMC particulate systems, release was sustained up to 10 hours. Hydrophobic HPMC with Na-Alg is an excellent matrix to formulate site-specific and controlled drug release particulate systems.

Este estudo teve como objetivo a obtenção de sistemas particulados para a liberação controlada de fármacos em sítios de ação específicos. Algumas partículas foram preparadas utilizando-se diferentes concentrações de alginato de sódio (Na-Alg) e outras foram formuladas por diferentes proporções de Na-Alg com estearoxílico éter de hidroxipropilmetilcelulose (HPMC) (grau de viscosidade 60M), uma forma hidrofóbica do convencional HPMC, utilizando o diclofenaco de potássio (DP) por métodos de troca iônica. Os grânulos foram caracterizados pela eficiência de encapsulação, perfil de liberação, inchaço e taxa de erosão. A adequação de diferentes modelos empíricos (de ordem zero, primeira ordem e Higuchi) e semi-empíricos (Ritger-Peppas e Peppas-Sahlin) foi estudada para descrever o perfil de liberação do fármaco. O modelo de Weibull também foi estudado. Os modelos foram testados através de ajuste não linear de curva pelo método dos mínimos quadrados. O software matemático MATLAB foi utilizado como ferramenta de análise matemática. Além disso, em vez do método de ajuste linear de dados transformados, foi utilizado o ajuste direto para evitar qualquer tipo de erro de truncamento ou de transformação. A cinética de liberação dos grânulos indicou liberação controlada puramente pelo processo de relaxamento, referida como transporte caso II. A distribuição de Weibull apresentou bom ajuste. A liberação do DP a partir de partículas de Na-Alg foi concluída em 5-6 horas, enquanto que a partir de sistemas particulados de Na-Alg HPMC hidrofóbico, a liberação foi mantida por até 10 horas. O HPMC hidrofóbico com Na-Alg é uma excelente matriz para a formulação de sistemas particulados para a liberação controlada de fármacos em sítios de ação específicos.

Preparation and in Vitro Drug Release Characteristics of Aspirin Gastric Floating Capsule / 中国药房

OBJECTIVE:To prepare aspirin gastric floating capsule and to study its in vitro drug-release characteristics.METHODS:Aspirin gastric floating capsule was prepared with aspirin as model drug,and with hydroxypropyl methylcellulose(HPMC)under different viscosity and different quantity and carbopol as main excipients.The release rate of the capsules was determined.RESULTS:When the optimal ratio between HPMC K4M and HPMC K15M was3to1,then the in vitro drug release of aspirin gastric floating capsule within0h～10h conformed to apparent zero-order kinetics with rate constant Kr at10.3%/h and release parameter at0.6173.CONCLUSIONS:The prepared capsule has a marked slow-release effect,the quantity and the viscosity of HPMC were the main factors affecting the release rate of gastric floating capsule,the in vitro drug release characteristics were associated with the joint action of bulk erosion and drug diffusion.

Preparation and evaluation of silymarin supersaturation self-emulsifying drug delivery system / 中草药

Objective To prepare the supersaturation self-emulsifying drug delivery system(S-SEDDS) containing silymarin and to evaluate its basic properties.Methods With the time of self-emulsifying,the consequence of color visual examination and particle size as parameters,the optimum formulations of silymarin SSEDDS were screened by solubility test,compatibility tests and pseudo ternary phase diagrams.The silymarin concentration was determined by HPLC.The in vitro dissolution characteristics of silymarin S-SEDDS were investigated with silymarin SEDDS as control.Results The optimum silymarin S-SEDDS was composed of medium chain triglycerides(MCT) 40%,Cremophor RH40(ethoxylated hydrogenatedcastor oil) 48%,Labrasol 12%.The time of self-emulsifying was less than 3 min,the average particle diameter was 49.6 nm,the adding amount of hydroxypropyl methylcellulose(HPMC) was 50 mg/g,and the average content of silymarin was 39.3 mg/g.The in vitro dissolution test of silymarin S-SEDDS showed that the presence of a small amount of cellulosic polymer effectively sustained a metastable supersaturated state by retarding precipitation kinetics.Conclusion The designed formulation of silymarin S-SEDDS is reasonable and provides a strong foundation for further development of new preparations.