Drug Release Properties of the Microcapsules of Adriamycin Hydrochloride with Ethylcellulose Prepared by a Phase Separation Technique

Abstract

Adriamycin hydrochloride was microencapsulated with ethylcellulose by a phase separation method to develop a prolonged release dosage form. Polyisobutylene (PIB) was used as a coacervation-inducing agent to control the particle size and drug release rate of the resultant microcapsules. With increasing the concentration of PIB (1 to 3 %) the average diameter of the microcapsules decreased, due to the fact that the microcapsules were discreted to a single microcapsule. At low concentration of PIB, the resultant microcapsules were agglomerated, which resulted in increasing the size. The microcapsules prepared with PIB 2 % prolonged desirably the drug release from the microcapsules. A little size effects of the microcapsules on the drug release rate was found for the microcapsules with PIB 2 % and 3 %.     

Influence of polyisobutylene on microencapsulation of metronidazole

Abstract

Metronidazole was microencapsulated with ethylcellulose by a phase separation method to develop a sustained release dosage form. Polyisobutylene (PIB) was used as a protective colloïd to control the particule size and the drug release of the microcapsules. The influence of PIB on microcapsules charateristics depends on the core-wall ratio, the molecular weight of PIB and the concentration of PIB.     

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.     

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.     

Preparation of embolic NEMs loading capecitabine

The nanoparticles-embedded microcapsules (NEMs) with smooth surface, good sphericity, excellent dispersivity and uniform particle size distribution were prepared by emulsification combined with electrospraying to extend the sustained release performance of the embolic microcapsules loading capecitabine (CAP). The sodium alginate and chitosan with good biocompatibility were used as the materials and CAP as a small-molecule model drug. The drug loading, encapsulation efficiency and drug release of CAP in the NEMs were investigated. The results showed that the drug-loading and encapsulation efficiency both increased with the increment of chitosan and CAP concentration. The maximum values of drug loading and encapsulation efficiency were 1.97 and 18.01 % respectively when initial CAP concentration was 5.0 g/L and chitosan molecular weight 100 kDa. The cumulative release rate of CAP released from the NEMs was lower than 30 % in 0.5 h, which indicated that there was no obvious initial burst release behavior. In the subsequent 240 h, the release results confirmed that the NEMs had better sustained release properties compared to pure microcapsules, and it might be a new anticancer drug delivery system in the future studies.     

Effects of hydrophilic excipients and compression pressure on physical properties and release behavior of aspirin-tableted microcapsules.

Aspirin ethylcellulose microcapsules were tableted by compression with or without excipients (lactose or polyvinylpyrrolidone [PVP]). The effects of the amount of the excipients and microcapsule size on the crushing strength and release rate of aspirin from tableted microcapsules were investigated. Tablets without excipients had a crushing strength that was independent of the applied pressure and microcapsule size. An increase in compression pressure from 15 to 60 MPa resulted in an increase in the crushing strength of tablets containing 20% or 40% w/w lactose, but the reverse results were obtained for the tableted microcapsules containing 20% or 40% w/w PVP. Results showed that the release rate of aspirin from microcapsules containing lactose or PVP was independent of the compression pressure with the exception of tablets containing 40% w/w lactose. In vitro release profiles of aspirin from tableted microcapsules containing lactose or PVP showed that increasing the concentration of the excipients resulted in an increase in the release rate of aspirin. Values of n were changed by the compression pressure and the added excipients.     

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.     

Preparation of Acetaminophen Microcapsules by Coaservation-Phase Separation Method

In this study, it was aimed to prepare prolonged action microcapsules of acetaminophen with short biological half-life by a non-solvent addition method which is one of the conservation-phase separation techniques.

For this purpose, the three different particle size ranges of acetaminophen (0.088-0.177 mn, 0.250-0.354 mn, 0.420-0.500 mn) were used. The solution of polyisobuthylene in cyclohexane as a non-solvent and Eudragit RS and Eudragit RL as coating polymers were also used. The prepared mi crosapsules were compressed by a hydraulic press using different types of direct tableting agents such as Ludipress, Avicel PH 101 and Lactose EP D 30. Dissolution rates of each tablet containing 160 mg of microencapsulated acetaminophen were examined by continuous flow-through cell method

The results of this study showed that the release rate of drug from microcapsules prepared with Eudragit RS was lower than that of microcapsules prepared with Eudragit RL. However different particle size ranges of drug didn't affect significantly the release rate; but different types of direct tableting agents were effective on the release rate of drug.     

Effects of Hydrophilic Excipients and Compression Pressure on Physical Properties and Release Behavior of Aspirin-Tableted Microcapsules

Aspirin ethylcellulose microcapsules were tableted by compression with or without excipients (lactose or polyvinylpyrrolidone [PVP]). The effects of the amount of the excipients and microcapsule size on the crushing strength and release rate of aspirin from tableted microcapsules were investigated. Tablets without excipients had a crushing strength that was independent of the applied pressure and microcapsule size. An increase in compression pressure from 15 to 60 MPa resulted in an increase in the crushing strength of tablets containing 20% or 40% w/w lactose, but the reverse results were obtained for the tableted microcapsules containing 20% or 40% w/w PVP. Results showed that the release rate of aspirin from microcapsules containing lactose or PVP was independent of the compression pressure with the exception of tablets containing 40% w/w lactose. In vitro release profiles of aspirin from tableted microcapsules containing lactose or PVP showed that increasing the concentration of the excipients resulted in an increase in the release rate of aspirin. Values of n were changed by the compression pressure and the added excipients.     

In vitro and in vivo evaluation of sustained-release and enteric-coated microcapsules of diclofenac sodium

This work examines the release of diclofenac sodium from ethylcellulose (EC) microcapsules made up of different drug to polymer ratios. The release process was found to follow the Higuchi square root equation and not the zero-order or first order equations. However, for drug to polymer ratio of 1:1, a critical time (θ) was reached beyond which the release rate was lower than that predicted on the basis of the Higuchi square root equation. Dissolution experiments in 0.1N HCL revealed that less than 1.5% of the encapsulated drug was released in 6 h. This finding indicates the suitability of the EC microcapsules for enteric-coated preparations. The in vitro release of diclofenac sodium from microcapsules of different drug to polymer ratios was compared with that from a commercial sustained-release product. A distinct similarity between the release profile of the commercial product with that obtained for the 1:2 drug to polymer microcapsules was noted. The in vivo work included determination of the serum drug profile following oral administration of the microcapsules and the commercial product to rabbits. The obtained serum concentration time profile of the EC microcapsules exhibited a sustained-release pattern similar to the commercial product and consistent with the in vitro results.     

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.     

聚氨基酸复合微胶囊对Hb的控制释放

以生物相容性好、价格低廉的海藻酸钠(ALG)为聚阴离子芯材,通过静电液滴装置制备了平均粒径在290 μm左右、球形度好、表面光洁的海藻酸钙胶珠;再将生物可降解、具有介入治疗作用的聚精氨酸(PLA)与聚组氨酸(PLH)的混合物作为聚阳离子壁材,在海藻酸钙胶珠表面覆上一层高分子聚合膜以制备聚氨基酸复合微胶囊;并以牛血红蛋白Hb为药物模型,对微胶囊的控制释放性能进行了考察并将其初步应用于体外模拟口服给药。结果表明:聚氨基酸复合微胶囊在前0.5 h的累积释放量均低于40％,溶出结束时累积释放量均达到80%以上;ALG/(PLA-PLH)复合微胶囊和ALG/PLH微胶囊的药物释放速率均低于ALG/PLA微胶囊;于10 min成膜时间内制备的微胶囊具有较高的载药量、包封率和缓释性能;以pH 4.6 HAc-NaAc缓冲液为成膜溶媒制备的微胶囊,Hb持续释放时间和残留量均高于蒸馏水组;前2 h在模拟胃液的pH 1.2 HCl溶媒中累计释放的Hb不超过10％且绝大部分是在模拟肠液环境即pH 6.8 PBS 溶媒中释放的;壳聚糖的引入能在一定程度上延长药物释放时间。聚氨基酸复合微胶囊具备一定的缓释性、pH响应性和生理黏附性,有望成为一种口服给药系统用药物载体。      

Development of an Emulsion-Solvent Evaporation Technique for Microencapsulation of Drus-Resin complexes

Chlorpheniramine maleate was complexed with a carboxylic acid cation-exchange resin and the complexes were microencapsulated with polymethyl methacrylate using an emulsion-solvent evaporation technique. Microcapsules of larger mean diameters resulted from polymer solutions of increased viscosities. Addition of 3% finely divided solids to the encapsulation vehicle resulted in smaller microcapsules, whereas a 6% concentration had the opposite effect, an increased capsule mean diameter. Emulsion stabilizers, such as magnesium stearate, up to a 1% concentration reduced microcapsule size by as much as 50%. The process efficiency ranged from 73% to 99%, depending on the formulation and manufacturing conditions used. The rate of drug release from the microcapsules was directly related to the amount of polymer deposited and inversely proportional to the capsule size.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^-2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Development of an Emulsion-Solvent Evaporation Technique for Microencapsulation of Drus-Resin complexes

Abstract

Chlorpheniramine maleate was complexed with a carboxylic acid cation-exchange resin and the complexes were microencapsulated with polymethyl methacrylate using an emulsion-solvent evaporation technique. Microcapsules of larger mean diameters resulted from polymer solutions of increased viscosities. Addition of 3% finely divided solids to the encapsulation vehicle resulted in smaller microcapsules, whereas a 6% concentration had the opposite effect, an increased capsule mean diameter. Emulsion stabilizers, such as magnesium stearate, up to a 1% concentration reduced microcapsule size by as much as 50%. The process efficiency ranged from 73% to 99%, depending on the formulation and manufacturing conditions used. The rate of drug release from the microcapsules was directly related to the amount of polymer deposited and inversely proportional to the capsule size.     

Controlled Release Kinetics of Captopril From Tableted Microcapsules

Abstract

Different viscosity grades ethylcellulose coated captopril microcapsules were prepared using temperature induced coacervation method from cyclohexane containing 2% Tween 80. Microcapsules were compressed directly into tablets. In vitro dissolution was carried out in 0.1 N HCl at 37°C using the rotating basket method. Release from tablets of all the batches was extensively prolonged in comparison to the respective microcapsules. The longest time for 70% drug release was shown by microcapsules (55min) and tablets (378 min) of the batch E-2. Release rate constants, correlation, determination and regression coefficients were calculated for the first-order, zero-order and Higuchi's equations. The best fit of release kinetics with the highest correlation and determination coefficients was achieved with the first-order followed by Higuchi's plot.     

In Vitro/in Vivo Evaluation Of A Liquid Sustained Release Dosage Form Of Chlorpheniramine

Chlorpheniramine-resin complexes were coated with cellulose acetate butyrate to yield microcapsules with a geometric mean diameter of 346 μm. In vitro release rate of chlorpheniramine declined with increasing microcapsule size. Release of chlorpheniramine from the micropcapsules was faster in simulated gastric fluid (pH 1.2) than in simulated intestinal fluid (pH 7.5). A Chlorpheniramine solution administered by rapid intravenous injection to dogs exhibited a two phase decline in plasma drug concentration. A peroral solution resulted in a rapid rise to a peak followed by a sharp decline in plasma chlorpheniramine concentration. Peroral administration of a microcapsule suspension caused a rapid rise in plasma concentration, but prevented the fast decline.     

Peculiar effect of polyethylene glycol in comparison with triethyl citrate or diethyl phthalate on properties of ethyl cellulose microcapsules containing propranolol hydrochloride in process of emulsion-solvent evaporation

Plasticizers play a crucial role in various process of microencapsulation. In this study, the effect of incorporation of plasticizer in process of emulsion solvent evaporation was investigated on properties of ethyl cellulose (EC) microcapsules containing propranolol hydrochloride. The effect of plasticizer type and concentration were investigated on characteristics of microcapsules prepared from different viscosity grades of EC. Product yield, encapsulation efficiency, mean particle size, shape, surface characteristics, solid state of drug, and drug release profiles were evaluated. Product yield and encapsulation efficiency were not dependent on plasticizer type and concentration. However, encapsulation efficiency decreased with increase in EC viscosity grade in the most of the cases. The mean particle size was in the range of 724–797?μm and was not dependent on plasticizer type. Microcapsules formed in the presence of PEG had a very smooth surface with few pores. XRD and DSC studies revealed a reduction of drug crystallinity after microencapsulation especially in presence of PEG. The results showed that the presence of TEC and DEP with different concentrations had no marked effect on drug release from microcapsules containing different viscosity grades of EC. This was not the case when PEG was used, and despite its water solubility it reduced the drug release rate noticeably. The reduction in the drug release in the presence of PEG was concentration-dependent. The use of PEG as a plasticizer in process of emulsion solvent evaporation highly improved the EC microcapsule structure and retarded the drug release rate and therefore is recommended.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Abstract

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^?2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Development of core-shell microcapsules by a novel supercritical CO2 process

5-fluorouracil-SiO₂-poly(L-lactide) (5-Fu-SiO₂-PLLA) microcapsules were prepared in a novel process of solution-enhanced dispersion by supercritical CO₂ (SEDS). The SiO₂ nanoparticles were loaded with 5-Fu by adsorption at the first place, then the 5-Fu-SiO₂ nanoparticles were coated with PLLA by a modified SEDS process. The resulted microcapsules were characterized by scanning electron microscope (SEM), laser diffraction particle size analyzer, Fourier transform infrared spectrometer (FTIR) and thermogravimeter-differential scanning calorimeter (TG-DSC). The drug load, encapsulation efficiency and drug release profiles were also determined. The resulted microcapsules exhibited a rather spherical shape, smooth surface, and a narrow particle size distribution with a mean particle size of 536 nm. The drug load and encapsulation efficiency of the samples were 0.18% and 80.53%, respectively, 25.05% of 5-Fu was released in the first half hour, then drug released in a sustained process, which was much slower than that of without coated by PLLA. The results indicated that the modified SEDS process could be used to produce drug-polymer microcapsules with a core-shell structure, high encapsulation efficiency and sustained drug release effect.