Modified release of coated sugar spheres using drug-containing polymeric dispersions

A drug-containing polymeric dispersion was applied onto nonpareil sugar spheres (18/20 mesh) using a fluid-bed spray coater. Eudragit RS30D was selected as the polymeric coating material. Melatonin secreted by the pineal gland in a circadian rhythm was used as a model drug. The release behaviors of the coated sugar spheres were investigated in gastric fluid (pH 1.4) for 2 h, and then continuously in intestinal fluid (pH 7.4) for 14 h. The release rate of the coated sugar spheres decreased with increasing coating levels. The solvent (ethanol) in the coating dispersions significantly decreased the release of the drug due to the good dispersion of the low solubility melatonin in the polymeric films. The polymer (polyvinylpyrrolidone, PVP) and drug contents in the coating dispersions did not affect the release rate. Most of all, the release profiles were drastically changed according to the type and concentration of plasticizers used. The current coating methods that use drug-containing polymeric dispersions could be useful for simultaneous drug loadings and their modified release. The solubilization and controlled release of poorly water-soluble drugs can be achieved as both the solubilizers and drugs are present in the drug-containing polymeric dispersions.     

Release behavior and photo-image of nifedipine tablet coated with high viscosity grade hydroxypropylmethylcellulose: effect of coating conditions

An orally applicable nifedipine-loaded core tablets was coated using high viscosity grade HPMC (100,000 cps) in ethanol/water cosolvent. The release of coated tablet was evaluated using USP paddle method in 900 ml of simulated gastric fluid (pH 1.2) for 2 h followed by intestinal fluid (pH 6.8) for 10 h. The surface morphologies using scanning electron microscope and photo-images using digital camera of coated tablet during the release test were also visualized, respectively. The viscosity of hydro-alcoholic HPMC solution largely decreased as the amount of ethanol increased. There was no significant difference in viscosity among plasticizers used. The distinct and continuous coated layer was observed using scanning electron microscope. However, the surface morphologies were highly dependent on HPMC concentration and ratio of coating solvents. The higher ratio of ethanol/water gave a longer lag time prior to drug release. Lag time also increased as a function of the coating levels based on weight gains due to increased thickness of coated layer. Lag time is inversely correlated with HPMC concentration in ethanol/water (5:1) cosolvent. As the HPMC concentration slightly decreased from 3.8 to 3.2% in hydroalcoholic coating solution, a large increase of lag time was observed. As the swelling (mixing) time of high viscosity grade HPMC in ethanol/water cosolvent increased from 1 to 5 h, the release rate was decreased due to enough plasticization of polymer. Based on photo-imaging analysis, the coated tablet was initially swelled and gelled without erosion and disintegration over 5 h. The disintegration of the coated tablet was occurred approximately 7 h after dissolution, resulting in pulsed release of drug. The high viscosity grade HPMC can be applicable for polymeric coating after careful selection of solvent systems. The release behavior and lag time could be controlled by coating conditions such as HPMC concentration, ethanol/water ratio as a coating solvent, coating level and swelling (mixing) time of coating solution. The current time-controlled release tablet coated with high viscosity grade HPMC with a designated lag time followed by a rapid release may provide an alternative to site specific or colonic delivery of drugs. In addition, the release behavior can be matched with body's circadian rhythm pattern in chronotherapy.     

Aqueous ethyl cellulose dispersions containing plasticizers of different water solubility and hydroxypropyl methylcellulose as coating material for diffusion pellets. I. Drug release rates from coated pellets

The present work investigates release mechanisms of theophylline pellets coated with an aqueous ethyl cellulose (EC) dispersion containing plasticizers and hydroxypropyl methylcellulose (HPMC) as a water soluble pore former. Three different drug release mechanisms from coated pellets can be determined as a function of the water solubility of the plasticizers and the ionic strength of the release medium. Coated pellets with the addition of more hydrophilic plasticizers such as triethyl citrate (TEC) or diethyl phthalate (DEP) show an approximate zero-order-release rate. In contrast, two-phase release profiles can be observed from pellets coated with dispersions containing hardly soluble plasticizers such as dibutyl phthalate (DBP) or dibutyl sebacate (DBS). Only in a release medium of high ionic strength the water soluble pore former will remain in the coating. Thus the drug diffuses through a hydrated swollen membrane containing EC, HPMC and insoluble plasticizer. The release mechanisms depend on the glass transition temperature of the ethyl cellulose and therefore on the migration of the plasticizers and the pore former. This was shown by investigation of the migration of the additives and the influence of the temperature of the release medium on the release. Additionally, the study investigates the effect of curing and storage conditions of coated pellets on the drug release rate.     

Characterization of 5-fluorouracil release from hydroxypropylmethylcellulose compression-coated tablets

Hydrogel compression-coated tablets are able to release the core drug after a period of lag time and have potential for colon-specific drug delivery based on gastrointestinal transit time concept. This study investigated the factors influencing in vitro release characteristics of a model drug 5-fluorouracil from hydroxypropylmethycellulose (HPMC) compression-coated tablets. The core tablet, prepared by a wet granulation compression method, was designed to disintegrate and dissolute quickly. To prepare the compression-coated tablets, 50% of the HPMC/lactose coat powder was precompressed first, followed by centering the core tablet and compressing with the other 50% of the coat powder. Release characteristics were evaluated in distilled water by using a Chinese Pharmacopoeia rotatable basket method. Effect of HPMC viscosity, lactose content in outer shell, and overall coating weight of outer shell on release lag time (T(lag)), and zero-order release rate (k) were studied. Release of drug from compression-coated tablets began after a time delay as a result of hydrogel swelling/retarding effect, followed by zero-order release for most of the formulations studied. HPMC of higher viscosity (K4M and K15M) provided better protection of the drug-containing core, showing increased release lag time and slower release rate. Incorporating lactose in outer shell led to decrease of T(lag) and increase of k. T(lag) and k are exponentially and linearly correlated to lactose content, expressed as weight percentage of the outer shell. Larger coating weight (W) of outer shell produced larger coating thickness (D) around core tablet, which resulted in increase in T(lag) and decrease in k. There was good fitting of a linear model for each of the four variables W, D, T(lag), and k. Hardness of the compression-coated tablets and pHs of the release media had little effect on drug release profile. It is concluded that the release lag time and release rate are able to be tailored through adjusting the formulation variables to achieve colon-specific drug delivery of 5-fluorouracil.     

Biphasic release characteristics of dual drug-loaded alginate beads

The dual drug-loaded alginate beads simultaneously containing drug in inner and outer layers were prepared by dropping plain (single-layered) alginate beads into CaCl₂ solution. The release characteristics were evaluated in simulated gastric fluid for 2 h followed by intestinal fluids thereafter for 12 h. The surface morphology and cross section of dual drug-loaded alginate beads was also investigated using scanning electron microscope (SEM). The poorly water-soluble ibuprofen was chosen as a model drug. The surface of single-layered and dual drug-loaded alginate beads showed very crude and roughness, showing aggregated particles, surface cracks and rough crystals. The thickness of dual drug-loaded alginate beads surrounded by outer layer was ranged from about 57 to 329μm. The distinct chasm between inner and outer layers was also observed. In case of single-layered alginate beads, the drug was not released in gastric fluid but was largely released in intestinal fluid. However, the release rate decreased as the reinforcing Eudragit^® polymer contents increased. When the plasticizers were added into polymer, the release rate largely decreased. The release rate of dual drug-loaded alginate beads was stable in gastric fluid for 2 h but largely increased when switched in intestinal fluid. The drug linearly released for 4 h followed by another linear release thereafter, showing a distinct biphasic release characteristics. There was a difference in the release profiles between single-layered and dual drug-loaded alginate beads due to their structural shape. However, this biphasic release profiles were modified by varying formulation compositions of inner and outer layer of alginate beads. The release rate of dual drug-loaded alginate beads slightly decreased when the outer layer was reinforced with Eudragit^® RS100 polymers. In case of dual drug-loaded alginate beads with polymer-reinforced outer layer only, the initial amount of drug released was low but the initial release rate (slope) was higher due to more swellable inner cores when compared to polymer-reinforced inner cores. The current dual drug-loaded alginate beads may be used to deliver the drugs in a time dependent manner.     

Development of sustained release fast-disintegrating tablets using various polymer-coated ion-exchange resin complexes

Complex formation between drugs and ion-exchange resins was investigated and the effects of coating by various aqueous polymeric dispersions on the complexes were evaluated for developing new sustained-release fast-disintegrating tablets (FDTs). Complexes of ion-exchange resin and dextromethorphan, a model drug, were prepared using different particle sizes of the resins. Aqueous colloidal dispersions of ethylcellulose (EC) and poly(vinyl acetate) (Kollicoat SR30D) were used for fluid-bed coating. Based on drug loading, release profiles, and scanning electron microscopy (SEM) images, the coated particles were granulated with suitable tablet excipients and then compressed into the tablets. Drug release profiles and SEM pictures were compared before and after the manufacturing processes. As the particle size of resins increased, the drug loading and release rate decreased due to the reduced effective diffusion coefficient and surface area. Higher coating level decreased the release rate further. In contrast to EC, Kollicoat SR30D coated particles could be compressed into tablets without any rupture or cracks on the coating since the mechanical properties of the polymer was more resistant to the manufacturing processes. This resulted in no significant changes in release rates. SEM showed the mechanical strength of the polymers affected the morphological change after compression. When the drug release profiles were applied into Boyd model and Higuchi equation, the linear relationship was observed, indicating that the diffusion within the resin matrix is the rate-controlling step.     

Characterization of 5-Fluorouracil Release from Hydroxypropylmethylcellulose Compression-Coated Tablets

Hydrogel compression-coated tablets are able to release the core drug after a period of lag time and have potential for colon-specific drug delivery based on gastrointestinal transit time concept. This study investigated the factors influencing in vitro release characteristics of a model drug 5-fluorouracil from hydroxypropylmethycellulose (HPMC) compression-coated tablets. The core tablet, prepared by a wet granulation compression method, was designed to disintegrate and dissolute quickly. To prepare the compression-coated tablets, 50% of the HPMC/lactose coat powder was precompressed first, followed by centering the core tablet and compressing with the other 50% of the coat powder. Release characteristics were evaluated in distilled water by using a Chinese Pharmacopoeia rotatable basket method. Effect of HPMC viscosity, lactose content in outer shell, and overall coating weight of outer shell on release lag time (T_lag), and zero-order release rate (k) were studied. Release of drug from compression-coated tablets began after a time delay as a result of hydrogel swelling/retarding effect, followed by zero-order release for most of the formulations studied. HPMC of higher viscosity (K4M and K15M) provided better protection of the drug-containing core, showing increased release lag time and slower release rate. Incorporating lactose in outer shell led to decrease of T_lag and increase of k. T_lag and k are exponentially and linearly correlated to lactose content, expressed as weight percentage of the outer shell. Larger coating weight (W) of outer shell produced larger coating thickness (D) around core tablet, which resulted in increase in T_lag and decrease in k. There was good fitting of a linear model for each of the four variables W, D, T_lag, and k. Hardness of the compression-coated tablets and pHs of the release media had little effect on drug release profile. It is concluded that the release lag time and release rate are able to be tailored through adjusting the formulation variables to achieve colon-specific drug delivery of 5-fluorouracil.     

Biphasic release of indomethacin from HPMC/pectin/calcium matrix tablet: II. Influencing variables, stability and pharmacokinetics in dogs

The pectin/calcium interaction, which is the basis for biphasic release of indomethacin from the HPMC/pectin/calcium chloride matrix tablet, is susceptible to influence of a variety of variables that is supposed to be encountered by the oral route. In this study, the effect of influencing variables on biphasic release characteristics, the stability and the pharmacokinetics of the hybrid matrix tablet were investigated. An increasing tendency of the overall release rate was observed from pH 1.2 to 7.4. The power law correlation n values increased with pH, while the release lag time or 10% release time (T_0.1) decreased at pH 6.8 and 7.4. Ionic strength in the release media also influenced the biphasic release significantly at sodium chloride levels of over 0.5%. Obvious increase in overall release rate was observed at sodium chloride level of 0.9% with an n value of 1.20 and a T_0.1 of 3.4 h. At sodium chloride levels of over 2%, the pectin/calcium interaction was disrupted resulting in very fast release of indomethacin. Release in gradient pH media was similar to that in pH 6.8 citrate buffer. When pectinase (Pectinex Ultra SP-L) was added into the release medium in 22.2 pg/ml or over, obvious triggering on drug release was observed. The stress testing showed increased release at extreme relative humidity of 92.5%. Both accelerated testing for 6 m and long-term testing for 12 m affirmed fine stability, especially in release characteristics. Pharmacokinetic study in dogs gave T_max/C_max of 4 h/604 ng/ml and 3 h/1662 ng/ml for HPMC/pectin/calcium and HPMC/pectin tablet, respectively. The plasma indomethacin level of the calcium-containing tablet was maintained at a much lower level for 3 h with a MRT of 7.13 h, longer than 3.97 and 5.61 h for indomethacin crude drug and HPMC/pectin tablet, confirming delayed absorption. The AUC of the HPMC/pectin/calcium tablet was lower than that of the HPMC/pectin tablet and indomethacin crude drug showing incomplete absorption. It is concluded that the HPMC/pectin/calcium matrix tablet is potentially useful for colon-specific drug delivery.     

Swellable matrices for the controlled-release of diclofenac sodium: formulation and in vitro studies

Oral administration has been the most usual and convenient employed route of drug delivery systems. Particularly, oral sustained-release systems for the delivery of drugs by a process of continuous swelling of the polymeric carrier have been investigated. Thus, the goal of this study was to evaluate the effects of hydroxypropyl methylcellulose (HPMC) and carboxypolymer (Carbopol 934) on the release behavior of diclofenac sodium (DS) from a swellable matrix tablet system. Nine different DS controlled-released tablets were compressed by using the wet-granulation technology. The influence of the polymer content, the polymer ratio, the polymeric swelling behavior, and the pH changes on the release rate of DS was investigated. There was no significant difference in drug release when total polymer concentration was 10%. When the tablets were formulated having 20% or 30% of HPMC/carbomer, it was observed that a more rapid release of DS occurred as the carboxypolymer ratio within the matrices increased. In agreement with previous results, the dissolution studies demonstrated that the combination of these two polymeric matrix formers resulted in near zero-order release rate of DS. The DS release from all these matrix tablets was pH dependent, being markedly reduced at lower pH, and could be attributed to the poor solubility of DS at this pH value. In HCl 0.1 N solution, HPMC controlled drug release because the carbomer has a low solubility at this pH. As the pH increased, the carbomer became ionized, being able to interact with HPMC to control the drug release.     

Optimization of propranolol HCl release kinetics from press coated sustained release tablets

Press-coated sustained release tablets offer a valuable, cheap and easy manufacture alternative to the highly expensive, multi-step manufacture and filling of coated beads. In this study, propranolol HCl press-coated tablets were prepared using hydroxylpropylmethylcellulose (HPMC) as tablet coating material together with carbopol 971P and compressol as release modifiers. The prepared formulations were optimized for zero-order release using artificial neural network program (INForm, Intelligensys Ltd, North Yorkshire, UK). Typical zero-order release kinetics with extended release profile for more than 12 h was obtained. The most important variables considered by the program in optimizing formulations were type and proportion of polymer mixture in the coat layer and distribution ratio of drug between core and coat. The key elements found were; incorporation of 31–38 % of the drug in the coat, fixing the amount of polymer in coat to be not less than 50 % of coat layer. Optimum zero-order release kinetics (linear regression r2 = 0.997 and Peppas model n value > 0.80) were obtained when 2.5–10 % carbopol and 25–42.5% compressol were incorporated into the 50 % HPMC coat layer.     

Effect of solvents on physical properties and release characteristics of monolithic hydroxypropylmethylcellulose matrix granules and tablets

Effect of solvents on physical characteristics and release characteristics of monolithic acetaminophen (APAP) hydroxypropylmethylcellulose (HPMC) matrix granules and tablets were examined. Various types and amounts of solvents were employed for granulation and cOAting. APAP and other excipients were mixed and were then wet-granulated in a high-speed mixer. The dried granules were then directly compressed and film-coated with low viscosity grade HPMC. As the amount of water increased, the size of granules also increased, showing more spherical and regular shape. However, manufacturing problems such as capping and lamination in tableting occurred when water was used alone as a granulating solvent. The physical properties of HPMC matrix granules were not affected by the batch size. The initial release rate as well as the amount of APAP dissolved had a tendency to decrease as the water level increased. Addition of nonaqueous solvent like ethanol to water resulted in good physical properties of granules. When compared to water/ethanol as a coating solvent, the release rate of film-coated HPMC matrix tablets was more sensitive to the conditions of coating and drying in methylene chloride/ethanol. Most of all, monolithic HPMC matrix tablet when granulated in ethanol/water showed dual release with about 50% drug release immediately within few minutes followed by extended release. It was evident that the type and amount of solvents (mainly water and ethanol) were very important for wet granulation and film-coating of monolithic HPMC matrix tablet, because the plastic deforming and fragmenting properties of material were changed by the different strengths of the different solvents.     

In Vitro Controlled Release of Alfuzosin Hydrochloride Using HPMC-Based Matrix Tablets and Its Comparison with Marketed Product

The present study is an attempt to formulate a controlled-release matrix tablet formulation for alfuzosin hydrochloride by using low viscous hydroxy propyl methyl cellulose (HPMC K-100 and HPMC 15cps) and its comparison with marketed product. Different batches of tablets containing 10 mg of alfuzosin were prepared by direct compression technique and evaluated for their physical properties, drug content, and in vitro drug release. All the formulations had a good physical integrity, and the drug content between the batches did not vary by more than 1%. Drug release from the matrix tablets was carried out for 12 hr and showed that the release rate was not highly significant with different ratios of HPMC K-100 and HPMC15cps. Similar dissolution profiles were observed between formulation F3 and the marketed product throughout the study period. The calculated regression coefficients showed a higher r² value with zero-order kinetics and Higuchi model in all the cases. Although both the models could be applicable, zero-order kinetics seems to be better. Hence, it can be concluded that the use of low viscous hydrophilic polymer of different grades (HPMC K-100 and HPMC 15cps) can control the alfuzosin release for a period of 12 hr and was comparable to the marketed product.     

Factors affecting drug release from drug-coated granules prepared by fluidized-bed coating

The preparation of drug-coated core formulations where the drug is located on the surface of a lactose granule core, using a methylcellulose (MC) or a hydroxypropylmethylcellulose (HPMC) polymeric system with diphenhydramine hydrochloride as a model drug, was studied. The drug and the polymer were applied onto lactose granules using the fluidized-bed coating method. The intermittent spray conditions adopted were able to minimize aggregation of the granules and the spray drying of the coating liquid. A high coating efficiency of over 97% was obtained and the granules were evenly coated. In vitro drug release from the coated granules was shown to be dependent on the drug loading, hydrophilicity, adhesive properties, viscosity and total amount of the polymer in the drug-polymer coat. The effect of the air entrapped in the coated lactose granules on their release profiles is also discussed. These results have important implications for the design of drug-coated granules as a modified-release dosage form employing a water-soluble polymeric system.     

Nanocapsule@xerogel microparticles containing sodium diclofenac: a new strategy to control the release of drugs

The aim of this work was to evaluate the potentiality to control the drug release of a new architecture of microparticles organized at the nanoscopic scale by assembling polymeric nanocapsules at the surface of drug-loaded xerogels. Xerogel was prepared by sol-gel method using sodium diclofenac, as hydrophilic drug model, and coated by spray-drying. After coating, the surface areas decreased from 82 to 28 m(2)/g, the encapsulation efficiency was 71% and SEM analysis showed irregular microparticles coated by the nanocapsules. Formulation showed satisfactory gastro-resistance presenting drug release lower than 3% (60 min) in acid medium. In water, the pure drug dissolved 92% after 5 min, uncoated drug-loaded xerogel released 60% and nanocapsule coated drug-loaded xerogel 36%. After 60 min, uncoated drug-loaded xerogel released 82% and nanocapsule coated drug-loaded xerogel 62%. In conclusion, the new system was able to control the release of the hydrophilic drug model.     

In vitro controlled release of alfuzosin hydrochloride using HPMC-based matrix tablets and its comparison with marketed product

The present study is an attempt to formulate a controlled-release matrix tablet formulation for alfuzosin hydrochloride by using low viscous hydroxy propyl methyl cellulose (HPMC K-100 and HPMC 15cps) and its comparison with marketed product. Different batches of tablets containing 10 mg of alfuzosin were prepared by direct compression technique and evaluated for their physical properties, drug content, and in vitro drug release. All the formulations had a good physical integrity, and the drug content between the batches did not vary by more than 1%. Drug release from the matrix tablets was carried out for 12 hr and showed that the release rate was not highly significant with different ratios of HPMC K-100 and HPMC15cps. Similar dissolution profiles were observed between formulation F3 and the marketed product throughout the study period. The calculated regression coefficients showed a higher r2 value with zero-order kinetics and Higuchi model in all the cases. Although both the models could be applicable, zero-order kinetics seems to be better. Hence, it can be concluded that the use of low viscous hydrophilic polymer of different grades (HPMC K-100 and HPMC 15cps) can control the alfuzosin release for a period of 12 hr and was comparable to the marketed product.     

Formulation development of Carvedilol compression coated tablet

Purpose: The aim of present research was to produce carvedilol compression coated tablet to provide biphasic drug release.

Method: A compressed coated tablet made of a sustained release core tablet and an immediate release coat tablet. Both the core and the coat contained carvedilol. The sustained release effect was achieved with polymers (HPMC K₄M and PEO WSR 205) to modulate the release of the drug. The powder blends for core and coat tablets were evaluated for angle of repose, bulk density, compressibility index, and drug content. Compressed coated tablets were evaluated for thickness, diameter, weight variation test, drug content, hardness, friability, disintegration and in vitro release studies.

Result: The powder blends showed satisfactory flow properties, compressibility, drug content and all the tablet formulations showed acceptable pharmaco-technical properties. Carvedilol contained in the fast releasing component was released within 3?min, whereas the drug in the core tablet was released at different times up to 24?h, depending on the composition of the matrix tablet. The mechanism of drug release was fickian diffusion or anomalous behavior.

Discussion: Batch F7, containing 10?mg PEO WSR 205 and 5?mg HPMC K₄M, showed maximum similarity with theoretical profile and zero order drug release kinetic.     

Biphasic release of indomethacin from HPMC/pectin/calcium matrix tablet: I. Characterization and mechanistic study.

Calcium-induced crosslinking of pectin acts as the dominating factor controlling drug release from pectin-based matrices. The same interaction was employed to modify indomethacin release from HPMC/pectin/calcium matrix in this study. The aim was to characterize the release profiles, and to study the formulation variables and the underlying mechanisms. The matrix tablet was made up of pectin HM 70, calcium chloride and HPMC K4M, and prepared by the wet granulation method. In vitro release was performed in water and characterized by the power law. Matrix erosion was evaluated by studying the weight loss and pectin release. Biphasic release of indomethacin from the HPMC/pectin/calcium matrix tablet was observed, and extraordinary power law exponent n values of over 1.0 were observed. Increase in calcium amount led to more significant retardation on drug release. The two power law parameters, n and K, correlated to the amount of calcium in the matrix. A lag time of over 4 h can be achieved at HPMC/pectin/calcium chloride amount of 100 mg/100 mg/100 mg. Both matrix weight loss and pectin release were linearly correlated to indomethacin release, indicating erosion-controlled drug release mechanisms. The hybrid matrix showed retarded erosion and hydration rate, which served as the basis for retarded indomethacin release. It is concluded that the pectin/calcium interaction can be employed to modify drug release from HPMC/pectin/calcium matrix tablet with biphasic release patterns for potential timed or site-specific drug delivery.     

A novel compression-coated doughnut-shaped tablet design for zero-order sustained release

A novel coated doughnut-shaped tablet is evaluated as to its ability to be manufactured in a reproducible manner, and as to whether it releases model drugs at a zero-order rate. The doughnut-shaped tablets were compressed using specially designed punches, which make automated production feasible. In the preliminary part of the experiment, HPMC K15M mixed with gelatin was found to be the most suitable coating tablet material with respect to its disintegration and adherence properties. The adherence of the coating tablet to ibuprofen cores was not optimal, so different concentrations of gelatin, to act as a plasticiser and enhance adherence, were further investigated. Friability results of the coated doughnut-shaped tablet indicate that coating tablets containing 20% and 30% gelatin had a percentage weight losses of less than 1% after 100 revolutions in a Roche friabilator. For all the concentrations of gelatin, the granule blends had angle of repose values in the range of 22.01-17.8 degrees. The compressibility factor, as measured from the slopes of the natural logarithm of compressional force versus crushing strength, were 121.91 +/- 2.36, 132.64 +/- 3.60, and 88.54 +/- 11.52 for the coating tablet granules containing 10%, 20%, and 30% gelatin in HPMC K15M, respectively. The composition of the coating tablet did not affect the rate of release of both caffeine and ibuprofen from the coated doughnut-shaped tablets. The coatings also adhered to the core tablets for the entire duration of the release of the drugs.     

磷酸川芎嗪膜控骨架缓释片的研制

目的 :以磷酸川芎嗪为模型药物 ,用乙基纤维素 -壳聚糖混合包衣液对其骨架片进行包衣 ,制备磷酸川芎嗪膜控骨架缓释片 ,以达到对该水溶性药物理想的缓释作用。方法 :用正交设计优选处方 ,以羟丙基甲基纤维素 (HPMC K1 0 0 M)为骨架材料 ,采用湿法制粒压片制备磷酸川芎嗪骨架片 ,用乙基纤维素 -壳聚糖混合包衣液进行包衣处理 ,以调节药物释放速度。用紫外分光光度法在2 95 nm测定吸收度 A来测主药含量 ,根据中国药典 2 0 0 0年版释放度测定法中转篮法测定其体外释放度 ,并对其稳定性作初步考察。结果 :所制备的薄膜包衣缓释片在 12 h内呈现良好的缓释特征 ,符合 Higuchi方程 ,Q=0 .0 95 3 t1 /2 -0 .0 3 87(r=0 .9874) ,且对湿、光、热稳定性良好。结论 :水不溶性材料乙基纤维素和水溶性材料壳聚糖 ,以适当比例混合使用作为包衣材料 ,结合骨架材料 ,对水溶性较大的药物能起到理想的缓释效果。     

Study of triethyl citrate migration from coating polymers to tablet cores

Migration of plasticizers from film coating polymers towards the core and to the storage medium could result in serious changes in the mechanical properties and permeability of coatings thus greatly influencing rate and extent of drug release. The purpose of the present study was to follow the migration of water soluble triethyl citrate applied as a plasticizer in Acryl-Eze coating by Gas Chromatography/Mass Spectrometry (GC/MS). 20%w/w Acryl-Eze dispersions containing triethyl citrate of different concentrations were prepared. Placebo tablets were compressed and coated with the prepared dispersions. The coated tablets were stored under different relative humidity conditions for different time intervals. Considerable migration of triethyl citrate towards the tablet cores was found. The extent of the triethyl citrate migration was influenced by the relative humidity of the storage medium.