Michoencapsulation and in Vitro Dissolution of Oxazepam from Ethyl Cellulose Microcapsules

Microcapsules of oxazepam with core:wall ratios 1:1 and 1:2 have been prepared by coacervation-phase separation method, using ethyl cellulose as a coating material. Phase separation was obtained by adding a salt solution to the dispersion of a water insoluble material in organic solution. Mioroencapsulation process protected oxazepam from photochemical decomposition and retarded its release. Release of the drug into simulated gastric and intestinal juice was studied. In vitro dissolution studies showed that first order release characteristics were exhibited.     

Oxazepam Dissolution Rate from Hydroxypropylmethylcellulose Matrices

The effect of some formulation variables on the release rate of oxazepam from hydroxypropylmethylcellulose (HPMC) has been investigated. The principal factors affecting this parameter were the content and molecular weight of HPMC, and the drug particle size. pH modified the oxazepam solubility; however, the liberation mechanism was not affected. The oxazepam release mechanism from these matrices has been examined. Values of the diffusional exponent n were in the range 0.61-0.74, indicating that the release of drug was controlled by both diffusion and erosion. When the tablets contained 30% HPMC K100 and the oxazepam particle size was 0.210-0.250 mm, near-zero-order kinetics was obtained (n = 0.85), indicating that erosion plays an important role in the oxazepam liberation.     

Tablet Properties and Dissolution Characteristics of Compressed Cellulose Acetate Butyrate Microcapsules Containing Succinyl Sulfathiazole

Cellulose acetate butyrate microcapsules of succinyl sulfathiazole were prepared by a modified emulsion-solvent evaporation method and formulated for compression with microcrystalline cellulose and carboxymethyl starch. Tablet hardness decreased and friability increased as microcapsule content increased. Formulations containing up to 50% microcapsules produced satisfactory tablets, but at 70% microcapsules, the tablets were unacceptably fragile. Variation of microcapsule size fraction from 75 μm up to 428 μm had only a small effect on tablet properties when formulated at the 40% level. Tablet hardness increased with increasing compression pressure from 1.9 kg at 17.6 MPa to 14.9 kg at 210.7 MPa. Dissolution properties of the microcapsules were essentially unchanged at compression pressures up to 351 MPa with T_50% values ranging from 121 to 132 minutes. Uncompressed microcapsules had a T_50% value of 130 minutes.     

Tablet Properties and Dissolution Characteristics of Compressed Cellulose Acetate Butyrate Microcapsules Containing Succinyl Sulfathiazole

Abstract

Cellulose acetate butyrate microcapsules of succinyl sulfathiazole were prepared by a modified emulsion-solvent evaporation method and formulated for compression with microcrystalline cellulose and carboxymethyl starch. Tablet hardness decreased and friability increased as microcapsule content increased. Formulations containing up to 50% microcapsules produced satisfactory tablets, but at 70% microcapsules, the tablets were unacceptably fragile. Variation of microcapsule size fraction from 75 μm up to 428 μm had only a small effect on tablet properties when formulated at the 40% level. Tablet hardness increased with increasing compression pressure from 1.9 kg at 17.6 MPa to 14.9 kg at 210.7 MPa. Dissolution properties of the microcapsules were essentially unchanged at compression pressures up to 351 MPa with T_50% values ranging from 121 to 132 minutes. Uncompressed microcapsules had a T_50% value of 130 minutes.     

A Study on the Manufacture and in Vitro Dissolution of Terbutaline Sulfate Microcapsules and their Tablets

Abstract

Microcapsules of terbutaline sulfate with cellulose acetate butyrate and ethylcellulose were prepared using an emulsion-solvent evaporation technique. The in vitro dissolution of terbutaline sulfate was studied using the USP rotating basket method. As the polymer to drug ratio increased, the microcapsule size distribution shifted to the smaller size and the release of terbutaline sulfate decreased. The release of terbutaline sulfate was independent of the dissolution medium pH for both polymers. The release kinetics from the microcapsules was dependent on the polymer type and polymer to drug ratio. The release of terbutaline sulfate from cellulose acetate butyrate and ethylcellulose microcapsules formulated with a 1:1 polymer to drug ratio was complex and could not be differentiated between the square-root of time and first-order release models. However, the square-root of time model was followed by microcapsules formulated with a 2:1 or a 3:1 cellulose acetate butyrate to drug ratio. When the ethylcellulose to drug ratio was increased to 2:1 the square-root of time model was followed. At an ethylcellulose to drug ratio of 3:1 the release kinetics could not be differentiated between the Hixon-Crowell and first-order release models. The T50% from ethylcellulose microcapsules was decreased when the microcapsules were compressed into tablets with the addition of Avicel^R/Emcompress^R (2:1) or Avicel^R.     

A Study on the Manufacture and in Vitro Dissolution of Terbutaline Sulfate Microcapsules and their Tablets

Microcapsules of terbutaline sulfate with cellulose acetate butyrate and ethylcellulose were prepared using an emulsion-solvent evaporation technique. The in vitro dissolution of terbutaline sulfate was studied using the USP rotating basket method. As the polymer to drug ratio increased, the microcapsule size distribution shifted to the smaller size and the release of terbutaline sulfate decreased. The release of terbutaline sulfate was independent of the dissolution medium pH for both polymers. The release kinetics from the microcapsules was dependent on the polymer type and polymer to drug ratio. The release of terbutaline sulfate from cellulose acetate butyrate and ethylcellulose microcapsules formulated with a 1:1 polymer to drug ratio was complex and could not be differentiated between the square-root of time and first-order release models. However, the square-root of time model was followed by microcapsules formulated with a 2:1 or a 3:1 cellulose acetate butyrate to drug ratio. When the ethylcellulose to drug ratio was increased to 2:1 the square-root of time model was followed. At an ethylcellulose to drug ratio of 3:1 the release kinetics could not be differentiated between the Hixon-Crowell and first-order release models. The T50% from ethylcellulose microcapsules was decreased when the microcapsules were compressed into tablets with the addition of Avicel^R/Emcompress^R (2:1) or Avicel^R.     

In Vitro Dissolution Profile of Theophvlline Lorded Ethvl Cellulose Microspheres Preprred by Emulsificrtion Soluent Eurporrtion

Theophylline was entrapped in ethyl cellulose microspheres by a water/oil/water emulsification-solvent evaporation method. Aqueous solution of drug was emulsified into a solution of ethyl cellulose in toluene, containing polyisobutylene as protective colloid, followed by emulsification of this primary emulsion into an external aqueous phase to form a water/oil/water emulsion. Microspheres was formed after solvent evaporation and precipitation of ethyl cellulose. In vitro dissolution profile and effect of polyisobutylene on it were studied.     

In Vitro Dissolution Profile of Theophvlline Lorded Ethvl Cellulose Microspheres Preprred by Emulsificrtion Soluent Eurporrtion

Abstract

Theophylline was entrapped in ethyl cellulose microspheres by a water/oil/water emulsification-solvent evaporation method. Aqueous solution of drug was emulsified into a solution of ethyl cellulose in toluene, containing polyisobutylene as protective colloid, followed by emulsification of this primary emulsion into an external aqueous phase to form a water/oil/water emulsion. Microspheres was formed after solvent evaporation and precipitation of ethyl cellulose. In vitro dissolution profile and effect of polyisobutylene on it were studied.     

Supercritical Antisolvent Precipitation of Ethyl Cellulose

Supercritical antisolvent (SAS) technique is an appropriate process to obtain micro- and nanoparticles. The application of this process has, until now, been explored in a variety of different fields including: explosives, polymers, pharmaceutical compounds, colouring matter, superconductors, catalysts, and inorganic compounds. Biocompatible and biodegradable polymers are playing more and more important roles in pharmaceutical areas such as tissue engineering and drug delivery. Formulation of these polymers into suitable solid-state forms plays an important role in safety, stability, and efficiency of the products. Ethyl cellulose is commonly used as drug carrier in controlled delivery systems. In this work, particles of ethyl cellulose have been precipitated by SAS using CO₂ as antisolvent and dichloromethane (DCM) as solvent. We studied the effects of concentration on the particle size distribution (PSD) of the precipitates. Ethyl cellulose size-controlled particles have been produced in the micrometer range 3.8–5.0 μm, and an increase of the mean particle diameter (MPD) was observed with the increase of the concentration of the solution.     

Dissolution Behavior of Oxazepam in Presence of Cyclodextrins: Evaluation of Oxazepam-Dimeb Binary Systemxs

The inclusion complex formation between oxazepam (Ox) and heptakis (2,6-di-O-methyl)-β-cyclodextrin (DIMEB) was studied in solution by solubility and ultraviolet spectroscopy methods, and in the solid state by differential scanning calorimetry, scanning electron microscopy, and powder x-ray diffractometry. The apparent stability constant, K_c, calculated by solubility and spectral data, was estimated as 642 and 588 M^-1, respectively. The solid complexes have been prepared by kneading and spray-drying techniques. The dissolution rate studies reveal that the better dissolution behavior corresponded to the spray-dried systems.     

Release Rate of Drugs from Ethyl Cellulose Coated Granules Containing Caffeine and Salicylic Acid

Abstract

Fluidized bed coating with ethyl cellulose., polyethylene glycol mixtures has been utilized for prolongation of drug release from granules containing salicylic acid and caffeine as model drugs. Drug release from the coated granules followed first order kinetics.

Particle size of the active material, granule composition and extraction medium pH did not affect the rate and kinetics of drug release. Increase in coat thickness decreased the release rate whereas elevation of the ratio of polyethylene glycol to ethyl cellulose enhanced the release rate to a degree related to the polyethylene glycol concentration. The permeability constants of salicylic acid and caffeine for the ethyl cellulose-polyethylene glycol coatings were of a similar order to those measured previously using solutions of the drugs with planar barrier films.     

In Vitro Release of Disopyramide from Cellulose Acetate Butyrate Microspheres

Disopyramide was microencapsulated with cellulose acetate butyrate (CAB) using an emulsion-solvent evaporation process. Drug dissolution from microcapsules was studied in both simulated gastric (SGF) and intestinal fluids (SIF) under sink conditions using the USP paddle method. There was no significant difference between drug release into SIF and SGF. As the CAB to drug ratio decreased from 3:1 to 2:1 at constant polymer mass, the drug release rate increased and the T50Y0 decreased from 2.3 hr to 0.3 hr for 303 pm particles. Dissolution T50% increased from 0.4 hr to 2 hr when the mean microcapsule size was increased from 153 to 428 μm (26% drug loading). The addition of acetone to the external phase during preparation shifted the size distribution toward larger particles, but resulted in a higher drug dissolution rate for a given particle size range. A shift to smaller particles was obtained upon increasing the concentration of surfactant. The dissolution profiles were described by the Higuchi and Baker-Lonsdale equations for drug release from spherical matrices up to 90% of the drug release.     

Release Rate of Drugs from Ethyl Cellulose Coated Granules Containing Caffeine and Salicylic Acid

Fluidized bed coating with ethyl cellulose., polyethylene glycol mixtures has been utilized for prolongation of drug release from granules containing salicylic acid and caffeine as model drugs. Drug release from the coated granules followed first order kinetics.

Particle size of the active material, granule composition and extraction medium pH did not affect the rate and kinetics of drug release. Increase in coat thickness decreased the release rate whereas elevation of the ratio of polyethylene glycol to ethyl cellulose enhanced the release rate to a degree related to the polyethylene glycol concentration. The permeability constants of salicylic acid and caffeine for the ethyl cellulose-polyethylene glycol coatings were of a similar order to those measured previously using solutions of the drugs with planar barrier films.     

Stabilization of Ethyl Cellulose against Photo Oxidation*

The determination of the sulphur in the silver bromide grains of a photographic emulsion shows that the sulphur contents are several times greater than that corresponding to the gelatin adsorbed to the grains. The significance of the sulphur atom for the occurrence of effective chemisorption is indicated.     

In Vitro Release of Disopyramide from Cellulose Acetate Butyrate Microspheres

Abstract

Disopyramide was microencapsulated with cellulose acetate butyrate (CAB) using an emulsion-solvent evaporation process. Drug dissolution from microcapsules was studied in both simulated gastric (SGF) and intestinal fluids (SIF) under sink conditions using the USP paddle method. There was no significant difference between drug release into SIF and SGF. As the CAB to drug ratio decreased from 3:1 to 2:1 at constant polymer mass, the drug release rate increased and the T50Y0 decreased from 2.3 hr to 0.3 hr for 303 pm particles. Dissolution T50% increased from 0.4 hr to 2 hr when the mean microcapsule size was increased from 153 to 428 μm (26% drug loading). The addition of acetone to the external phase during preparation shifted the size distribution toward larger particles, but resulted in a higher drug dissolution rate for a given particle size range. A shift to smaller particles was obtained upon increasing the concentration of surfactant. The dissolution profiles were described by the Higuchi and Baker-Lonsdale equations for drug release from spherical matrices up to 90% of the drug release.     

Comparison of In Vitro Dissolution and Permeation of Fluconazole from Different Suppository Bases

Fluconazole suppositories were prepared in hydrophilic, lipophilic, and amphiphilic bases. In vitro evaluation was conducted to compare the effect of different bases on the release and permeation of fluconazole. Four types of suppository bases were evaluated: hydrophilic (polyethylene glycol, PEG), lipophilic (cocoa butter, CB; Witepsol W45® WW45), and amphiphilic (Suppocire AP® SAP, a polyglycolized glyceride). The uniformity of dosage units prepared with each base was determined by ultraviolet (UV) spectroscopy. The influence of suppository base on the release of fluconazole was studied using USP dissolution apparatus I. Rate constants for each release pattern were determined and compared using a one-way analysis of variance (ANOVA) on ranks. The order of in vitro dissolution of fluconazole from the bases was as follows: PEG > (SAP = WW45) > CB. Results suggest that in vitro release of fluconazole is greater from a hydrophilic base (PEG). Preliminary permeation studies were conducted on each type of base using Franz diffusion cells. Permeation was studied through the rat rectal membrane, and normal saline was used as the receptor medium. A modified reverse-phase high-performance liquid chromatography (HPLC) method was used and validated for analyzing fluconazole. Flux values (μg/cm²/hr) were calculated and compared using a one-way ANOVA (p <. 001). The order of permeation was as follows: SAP > (PEG = WW45) > CB. The increased permeation characteristics seen with the SAP base are probably due to an alteration of the membrane characteristics due to the surface active properties of the base.     

纤维素在1-烯丙基-3-甲基咪唑氯盐中溶解机理

通过分析纤维素/1-烯丙基-3-甲基咪唑氯盐(AmimCl)溶液在不同温度下浊度的变化和红外谱图变化,研究了纤维素在AmimCl中的溶解机理。温度升高,浊度变大,红外谱图羟基特征峰向高波数移动,说明纤维素与AmimCl的相互作用是氢键,而且温度升高会破坏纤维素/AmimCl溶液中的氢键,从而导致纤维素在AmimCl中析出。向纤维素/AmimCl溶液加入尿素、LiCl、KH_2PO_2、K_2SO_4和KPF_6等不同的氢键受体,用核磁共振方法研究了这些氢键受体与AmimCl的相互作用,核磁研究表明,氢键受体与AmimCl相容性越好,溶解纤维素能力越大,进一步说明了纤维素与AmimCl间的氢键作用。根据这一结论,指导合成了3种新型离子液体,并考察了这些溶剂体系对于纤维素的溶解性。     

磷酸酯类离子液体对纤维素溶解性能的研究

采用一步法合成了两种磷酸酯类离子液体:1,3-二甲基咪唑磷酸二甲酯盐([MMIM]DMP)和1-乙基-3-甲基咪唑磷酸二乙酯盐([EMIM]DEP),并比较了它们对纤维素的溶解性能。结果表明,两种离子液体均能在一定条件下溶解纤维素,而[EMIM]DEP表现出较优的溶解能力,再生得到纤维素膜;随着溶解温度的升高,溶解时间缩短。采用红外光谱(FT-IR)、热重失重(TGA)分析、X射线衍射(XRD)、扫描电镜(SEM)等对再生前后的纤维素进行了表征。结果表明,未经活化的纤维素可直接溶于离子液体中而不发生其它衍生化反应;溶解再生后的纤维素晶型发生变化;经[EMIM]DEP溶解再生后纤维素热稳定性和聚合度下降较小,再生纤维素膜结构致密均一。     

DMSO对纤维素在咪唑型离子液体中溶解性能的影响

本文通过向传统离子液体中添加助溶剂DMSO来增强离子液体对纤维素的溶解效果。系统研究了DMSO添加量对纤维素溶解性能的影响,结果表明50℃下随着DMSO添加量的增大,纤维素的溶解程度增加,当DMSO添加量为50%时溶解效果最佳。采用电导率测试研究了DMSO与离子液体的作用机理,并通过FT-IR、XRD、TGA、SEM以及力学性能测试等方法对添加不同量DMSO溶剂溶解再生后的纤维素膜进行了分析,结果表明添加DMSO后溶剂仍为纤维素的直接溶剂,溶解再生后纤维素晶型由Ⅰ转变为Ⅱ型,并且随着DMSO添加量的增加,溶剂对纤维素分子链及结晶区的破坏能力增大,从而导致再生纤维素结晶度、抗拉强度及聚合度相对纯离子液体再生的有所降低。