Effect of Spheronization Technique on Drug Release from Uncoated Beads

Spheronization techniques are finding increased utility in pharmaceutical research and production. In this investigation emphasis is on the effect of two different spheronization methods (pan versus marumerizer) on drug release from uncoated beads containing acetaminophen and microcrystalline cellulose at a 1:1 ratio. Drug release from the pan beads is much faster than that from the marumerizer beads. The pan beads disintegrate during the dissolution testing, while beads made via the extruder and marumerizer appear to behave as an inert matrix system.     

Drug Release from Spray Layered and Coated Drug-Containing Beads: Effects of pH and Comparison of Different Dissolution Methods

Based on dissolution profiles of three model drugs on spray layered beads with the same percentage of Aquacoat® coating, it was concluded that in vitro dissolution of oral controlled–release formulations should be performed in both gastric and intestinal media for ionizable drugs. Ketoprofen (weak acid, pK_a 4.8), nicardipine HCl (salt of weak organic base, pK_a8.6), and acetaminophen (very weak organic acid, pK_a9.7, not ionized at physiologic pH) provided different dissolution characteristics in enzyme–free simulated gastric fluid (pH 1.4) and enzyme–free simulated intestinal fluid (pH 7.4), indicating that the rate of drug release was pH dependent and related to drug ionization even though the solubility of the coating (ethylcellulose) is pH independent. In acidic media, ketoprofen release from the beads containing low–level coating (3%) was slower than that of nicardipine HCl, with the opposite holding true in basic media. Acetaminophen was released at approximately the same rate in both acidic and basic media. A comparison of drug release profiles for nicardipine HCl nude beads was also investigated among three different dissolution methods: USP dissolution apparatus I (basket method, 50 rpm), USP dissolution apparatus II (paddle method, 50 rpm), and USP dissolution apparatus III (Bio–Dis®, Van–Kel Industries, 5 and 10 dpm). Release profiles obtained from all methods were similar, indicating that the three dissolution methods were comparable.     

Preparation and Dissolution Characteristics of Prolonged Release Mebeverine-HCL Beads

Different batches of slow release mebeverine-HCl beads were prepared by pan coating technique using different release retarding polymers viz Eudragit RL₁₀₀, Eudragit RS₁₀₀ and Ethyl cellulose. The thickness of the coats was controlled by changing the amounts of the added polymers. Pre- and overcoating of the beads with bees wax was also carried out. Mixtures of pre-waxed Eudragit RS₁₀₀ coated and uncoated beads in different ratios were prepared to control both drug content and release.

Dissolution profiles of mebeverine HCl from the prepared beads were investigated using USP XX rotating basket method. Prolonged release of mebeverine-HCl was obtained from different batches of the coated beads with the advantage of no initial dumping of the water soluble drug. The release of mebeverine-HCl from the beads coated with acrylic resins and ethyl cellulose as well as waxed acrylic resins coated beads was diffusion controlled according to Higuchi model. Beads coated with ethyl cellulose showed a different release pattern when pre-or overcoated with wax. By altering the ratios of prewaxed Eudragit Rs₁₀₀ coated and uncoated beads in formulated mixtures, it was possible to control both mebeverine-HCl content and release rate.     

Preparation and Dissolution Characteristics of Prolonged Release Mebeverine-HCL Beads

Different batches of slow release mebeverine-HCl beads were prepared by pan coating technique using different release retarding polymers viz Eudragit RL₁₀₀, Eudragit RS₁₀₀ and Ethyl cellulose. The thickness of the coats was controlled by changing the amounts of the added polymers. Pre- and overcoating of the beads with bees wax was also carried out. Mixtures of pre-waxed Eudragit RS₁₀₀ coated and uncoated beads in different ratios were prepared to control both drug content and release.

Dissolution profiles of mebeverine HCl from the prepared beads were investigated using USP XX rotating basket method. Prolonged release of mebeverine-HCl was obtained from different batches of the coated beads with the advantage of no initial dumping of the water soluble drug. The release of mebeverine-HCl from the beads coated with acrylic resins and ethyl cellulose as well as waxed acrylic resins coated beads was diffusion controlled according to Higuchi model. Beads coated with ethyl cellulose showed a different release pattern when pre-or overcoated with wax. By altering the ratios of prewaxed Eudragit Rs₁₀₀ coated and uncoated beads in formulated mixtures, it was possible to control both mebeverine-HCl content and release rate.     

Preparation and Evaluation of Controlled Release Propranolol Hydrochloride Beads

Conventional pan coating method was utilized to prepare propranolol-HCl sustained release coated beads. Eudragit RS 100 was used as release controlling materials. Overcoating of the beads with beeswax was also investigated. The beads were characterized for their particle size distribution, drug loading efficiency and their dissolution behaviour in 0.1N HCl, Most of the finished beads (72.4%) fall in the particle size range 800-1700 um. The actual drug content, calcu-lated as opposed to the theoretical drug content were 77.6% and 74.2% of the drug for the beads having particle size range 1700-1250 um and 1250-800 um respectively, The coating level of the polymer, the particle size of the beads and overcoating with beeswax play a major role in determining the release rate of the drug from the coated beads.     

Preparation and Evaluation of Controlled Release Propranolol Hydrochloride Beads

Abstract

Conventional pan coating method was utilized to prepare propranolol-HCl sustained release coated beads. Eudragit RS 100 was used as release controlling materials. Overcoating of the beads with beeswax was also investigated. The beads were characterized for their particle size distribution, drug loading efficiency and their dissolution behaviour in 0.1N HCl, Most of the finished beads (72.4%) fall in the particle size range 800–1700 um. The actual drug content, calcu-lated as opposed to the theoretical drug content were 77.6% and 74.2% of the drug for the beads having particle size range 1700–1250 um and 1250–800 um respectively, The coating level of the polymer, the particle size of the beads and overcoating with beeswax play a major role in determining the release rate of the drug from the coated beads.     

Thermal Treatment of Beads with Wax for Controlled Release

Abstract

Beads prepared by extruder/marumerizer technology were formulated with water soluble drugs, microcrystalline cellulose and several waxy materials. The waxes (10 to 50% by weight) were included in an effort to slow drug release. Subsequent thermal treatment of these beads was applied. Beads were processed to determine the effect of varying wax level, excipient, active drug, and effect of heat treatment. In-vitro drug release profiles were evaluated for the untreated and thermal treated beads. In general, the simple incorporation of wax into the granulation did not provide the desired controlled release dissolution profile. Thermal treatment of the finished beads, however, resulted in products which behaved in a different manner during dissolution testing and in general provided slower release. Drug release was found to vary with the type and level of wax, drug, excipient, and the thermal treatment.     

Thermal Treatment of Beads with Wax for Controlled Release

Beads prepared by extruder/marumerizer technology were formulated with water soluble drugs, microcrystalline cellulose and several waxy materials. The waxes (10 to 50% by weight) were included in an effort to slow drug release. Subsequent thermal treatment of these beads was applied. Beads were processed to determine the effect of varying wax level, excipient, active drug, and effect of heat treatment. In-vitro drug release profiles were evaluated for the untreated and thermal treated beads. In general, the simple incorporation of wax into the granulation did not provide the desired controlled release dissolution profile. Thermal treatment of the finished beads, however, resulted in products which behaved in a different manner during dissolution testing and in general provided slower release. Drug release was found to vary with the type and level of wax, drug, excipient, and the thermal treatment.     

琼脂糖醋酸酯纳米粒子的制备及药物缓释性

通过纳米沉淀法制备了一种粒径均一的琼脂糖醋酸酯纳米粒子,并对影响粒径的相关因素进行了研究。结果表明,纳米粒子分别随着二甲基亚砜(DMSO)与水的比率、姜黄素含量及琼脂糖醋酸酯(AA)的浓度的增加而增大,随转速的增加而下降,异丙醇和聚乙烯醇(PVA)浓度也有一定的影响。同时研究了载体对姜黄素的包载情况及缓释行为。结果显示,无异丙醇组中姜黄素载药率和包封率均比异丙醇组中的高。但两组都表明,随着姜黄素的含量增加,载药粒子的载药率不断增加,包封率不断降低。载药粒子大大延长了姜黄素的缓释时间。获得的琼脂糖醋酸酯纳米粒子可望用于姜黄素的控释。     

Controlled Drug Release from a Compressed Heterogeneous Polymeric Matrix: Kinetics of Release

A physical model of a new matrix-type system is presented where constant drug release can be maintained irrespective of the extent of the tortuosity and receding drug boundary. Theophylline base was dispersed as discrete crystals and fine particles in a matrix formed by the cross-linking of polymeric mixtures consisting of PEG, acrylic resins and ethyl cellulose. DSC analysis was performed to identify any solid state inactivation of the drug. Concave tablets at specified pressures were prepared in order to achieve a wide range of release rates and patterns of release. It was found that the patterns of release could be controlled by the formulation components and the manufacturing procedures. Drug release rates were determined spectrophotometrically under sink conditions and the flux of drug release, dQ/dt, from these matrix-type delivery systems was almost constant over 15 hours, during which time about 85% of the active drug was released. The release rate was devoid of any hydrodynamic boundary effect and environmental pH. The cumulative amount of drug released was found to be in accordance with zero-order kinetics. The system can be modified within broad limits and have flexibility as well as a wide spectrum of applicability with respect to different types of drugs.     

Controlled Drug Release from a Compressed Heterogeneous Polymeric Matrix: Kinetics of Release

A physical model of a new matrix-type system is presented where constant drug release can be maintained irrespective of the extent of the tortuosity and receding drug boundary. Theophylline base was dispersed as discrete crystals and fine particles in a matrix formed by the cross-linking of polymeric mixtures consisting of PEG, acrylic resins and ethyl cellulose. DSC analysis was performed to identify any solid state inactivation of the drug. Concave tablets at specified pressures were prepared in order to achieve a wide range of release rates and patterns of release. It was found that the patterns of release could be controlled by the formulation components and the manufacturing procedures. Drug release rates were determined spectrophotometrically under sink conditions and the flux of drug release, dQ/dt, from these matrix-type delivery systems was almost constant over 15 hours, during which time about 85% of the active drug was released. The release rate was devoid of any hydrodynamic boundary effect and environmental pH. The cumulative amount of drug released was found to be in accordance with zero-order kinetics. The system can be modified within broad limits and have flexibility as well as a wide spectrum of applicability with respect to different types of drugs.     

SiO2基药物可控释放材料

综述了SiO2基药物可控释放材料,分析了简单、掺杂、杂化SiO2药物可控释放凝胶,以及介孔SiO2药物可控释放材料的特点,讨论了水和前驱物的比例、催化剂、掺杂剂、凝胶前驱物的种类、凝胶比表面积与孔径、凝胶尺寸及药物负载量、以及药物与凝胶基质及掺杂剂之间的相互作用对可控释放的影响.对于SiO2基药物可控释放材料来说,基质溶胀和基质溶解对药物可控释放的影响不大,药物扩散是释放的主要机制.基于介孔SiO2的pH敏感和光敏开关效应,为SiO2基药物可控释放材料提供了新思路.     

A Sustained Release Drug Delivery System Using Calcium Alginate Beads

Abstract

Calcium alginate beads impregnated with sulphamethoxazole as model drug were prepared and characterized. Scanning electron microscope was used to examine their surface with and without the drug. The bead average diameter was 1.25mm and the sulphamethoxazole uptake by the beads was about half of the incorporated quantity. The release behaviour was followed using USP dissolution method. The effect on release of factors such as sodium alginate, calcium chloride concentration, pH, hydration and compression were studied. Sodium alginate concentrations had no pronounced effect on the release. The release was found to be a function of calcium chloride concentration. The higher the concentration the lower the release. The smaller the water content the lower the release from the beads. Compression of the beads yields a deformed beads with an increase in their release. Plain calcium alginate beads were not suitable for sulphamethoxazole loading. Sulphamethoxazole diffusion through calcium alginate film was determined. The dissolution patterns were discussed. The system may offer a simple and efficient sustain release preparation.     

Mathematical Simulation of Controlled Drug Release from Cylindrical Matrix Devices

Abstract

The general mathematical model for controlled drug release from the cylindrical matrix device was developed. The system under consideration is composed of an active agent which is dissolved homogeneously in a cylindrical porous matrix device. The method of lines was employed to solve the partial differential equation in the present study.

The effects of hydrodynamic diffusion layer, the rate of spontaneous decay reaction in the device, the height to radius ratio of the device and the porosity distribution in the device on the rate of drug release were investigated by solving the two dimensional diffusion equation under non-steady state conditions.

The results indicated that the release rate may be significantly underevaluated if the data obtained in the in vitro studies under a poor mixing condition are analyzed mistakenly on the assumption of well mixing condition.

The findings in the present analysis are of practical significance to the design and development of matrix-diffusion type controlled release drug products.     

A Sustained Release Drug Delivery System Using Calcium Alginate Beads

Calcium alginate beads impregnated with sulphamethoxazole as model drug were prepared and characterized. Scanning electron microscope was used to examine their surface with and without the drug. The bead average diameter was 1.25mm and the sulphamethoxazole uptake by the beads was about half of the incorporated quantity. The release behaviour was followed using USP dissolution method. The effect on release of factors such as sodium alginate, calcium chloride concentration, pH, hydration and compression were studied. Sodium alginate concentrations had no pronounced effect on the release. The release was found to be a function of calcium chloride concentration. The higher the concentration the lower the release. The smaller the water content the lower the release from the beads. Compression of the beads yields a deformed beads with an increase in their release. Plain calcium alginate beads were not suitable for sulphamethoxazole loading. Sulphamethoxazole diffusion through calcium alginate film was determined. The dissolution patterns were discussed. The system may offer a simple and efficient sustain release preparation.     

Mathematical Simulation of Controlled Drug Release from Cylindrical Matrix Devices

The general mathematical model for controlled drug release from the cylindrical matrix device was developed. The system under consideration is composed of an active agent which is dissolved homogeneously in a cylindrical porous matrix device. The method of lines was employed to solve the partial differential equation in the present study.

The effects of hydrodynamic diffusion layer, the rate of spontaneous decay reaction in the device, the height to radius ratio of the device and the porosity distribution in the device on the rate of drug release were investigated by solving the two dimensional diffusion equation under non-steady state conditions.

The results indicated that the release rate may be significantly underevaluated if the data obtained in the in vitro studies under a poor mixing condition are analyzed mistakenly on the assumption of well mixing condition.

The findings in the present analysis are of practical significance to the design and development of matrix-diffusion type controlled release drug products.     

Dissolution Characteristics of Capsule Shells and Drug Release from Commercial Tetracycline-Hcl Capsules

Abstract

The dissolution characteristics of the gelatin shells of four brands of tetracycline-HCl capsules were examined by measuring the shell rupture time (t_r) in a modified version of two-blade stirrer apparatus under various stirrer depth, ionic strength, and pH conditions. The dissolution rate of tetracycline-HCl from these capsules was also determined using the U.S.P. XIX dissolution apparatus. While no significant effect of stirrer depth on t_r was found, increasing the basket-stirrer distance from the bottom of the flask from 0.2 to 2 cm was found to increase the dissolution rate of tetracycline-HCl from capsules significantly (p < 0.001). As the ionic strength was increased, the dissolution rates of both gelatin shell and tetracycline-HCl content were increased, however, increasing the ionic strength from 0.6 to 1.5 failed to produce any further increase in t_r. The pH of the dissolution fluid significantly (p < 0.01) influenced the dissolution rate of the capsule shell and t_r was longest at pH = 4. A linear, inverse relationship between pH and tetracycline-HCl dissolution rate constant (k_s) was obtained. While a good correlation between t_r and k_s was obtained under certain conditions, capsule shell and tetracycline-HCl content showed different dissolution behaviour under other conditions. It is expected therefore, that under the latter conditions capsule shells had their maximum effect on drug release from the capsules studied.     

Optimization of Controlled Drug Release Through Micropelletization

Abstract

Micropelletization technique using crosslinked gelatin matrix was chosen to evaluate its utility in controlled release medications. Trimethoprim, which has a very high solubility gradient in gastric pH, was selected in this investigation. Micropellets were formed by the modified spray congealing technique. The effects of exposure of the crosslinking agents to the gelatin matrix of the micropellets on the effectivity as the controlled release drug delivery system were investigated. The total product yield, content uniformity and the reproducibilty of the sucessive batches were decidedly superior to either the pure drug or the non-crosslinked ones. Particle size distribution was observed to vary depending on the content of the crosslinked gelatin in the micropellets. Scanning electron micrographs confirmed the porous surface topography of the micropellets. The drug release characteristics was suggested as the diffusion controlled first order dissolution process.     

Comparison of Three Dissolution Devices for Evaluating Drug Release

Abstract

The dissolution studies are usually conducted on “official” USP dissolution devices or “non-official” dissolution devices like the Rotating Bottle Apparatus. The recent introduction of the Bio-Dis® Tester exacerbates a difficult situation : no comparative dissolution studies have been done regarding the results for a drug and/or dosage form using these three different instruments. The purpose of this investigation was to evaluate and compare three dissolution devices - USP XXI Dissolution Apparatus II, Rotating Bottle Apparatus, and Bio-Dis® Tester -taking into account pertinent factors that can affect dissolution. Dissolution profiles were obtained for two drugs - theophylline and phenylpropanolamine HCI. Three dosage forms of each drug were evaluated at different agitation intensities using two different dissolution media (simulated gastric fluid and simulated intestinal fluid) on all three dissolution devices. Various advantages/limitations for each device were observed depending on the drug, dosage form, agitation speed and dissolution medium.