Controlled release of dual drug-loaded hydroxypropyl methylcellulose matrix tablet using drug-containing polymeric coatings.

A dual drug-loaded hydroxypropylmethylcellulose (HPMC) matrix tablet simultaneously containing drug in inner tablet core and outer coated layer was formulated using drug-containing aqueous-based polymeric Eudragit RS30D dispersions. Effects of coating levels, drug loadings in outer layers, amount and type of five plasticizers and talc concentration on the release characteristics were evaluated on the characteristics in simulated gastric fluid for 2 h followed by a study in intestinal fluids. Melatonin (MT) was selected as a model drug. The surface morphology of dual drug-loaded HPMC tablets using scanning electron microscope (SEM) was smooth, showing the distinct coated layer with about 75-microm coating thickness at the 15% coating level. Unlike the uncoated and conventionally coated HPMC tablet, the dual drug-loaded HPMC matrix tablet gave a biphasic linear release, showing a zero-order for 4 h (first) followed by another zero-order release when fitted using linear regression (r(2) = 0.99). As the coating levels (15, 25%) increased, the release rate was further decreased. The biphasic release profiles of dual drug-loaded HPMC matrix tablet was unchanged except when 25% coating level containing 0.5% drug concentration was applied. As the drug concentration in polymeric coating dispersion increased (0.25-1.0%), the amount of drug released increased. The time for the first linear release was also advanced. However, the biphasic release pattern was not changed. The biphasic release profiles of dual drug-loaded HPMC matrix tablet were highly modified, depending on the amount and type of five plasticizers. Talc (10-30%) in coating dispersion as an anti-sticking material did not affect the release profiles. The current dual drug-loaded HPMC matrix tablet, showing biphasic release profiles may provide an alternative to deliver drugs with circadian rhythmic behaviors in the body but needs to be further validated in future in human studies. The dual drug-loaded coating method is also interesting for the modified release of poorly water-soluble drugs because solubilizers and other additives can be added in drug-containing polymeric coating dispersions.     

阿莫西林脉冲释药微丸的研制

目的:制备阿莫西林脉冲释药微丸。方法:取空白丸芯分别以含药层、溶胀层(羧甲基淀粉钠)和控释层(乙基纤维素水分散体)顺序依次进行包衣制备阿莫西林脉冲释药微丸。采用紫外法和篮法考察溶胀层(12%、16%、20%)和控释层包衣增重(24%、28%、32%)及不同介质(水、盐酸、pH6.8磷酸盐缓冲液)对药物释放的影响。结果:溶胀层和控释层包衣增重对脉冲控释微丸的释药时滞和释放速率具有显著影响,药物释放情况不受介质pH值的影响;溶胀层和控释层包衣增重分别为16%、28%时制备的微丸时滞时间约为4h,时滞后4h累积释药率达到80%。结论:所制备的阿莫西林脉冲释药微丸具有体外脉冲释放作用。     

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.     

Influence of film additives on stabilizing drug release rates from pellets coated with acrylic polymers.

The objective of this study was to investigate the influence of talc and triethyl citrate (TEC) on stabilizing the drug release rates following curing and storage at elevated temperature of pellets coated with an aqueous acrylic polymeric dispersion. Core pellets containing anhydrous theophylline (20%), microcrystalline cellulose, and polyvinylpyrrolidone were prepared by extrusion-spheronization. The aqueous dispersions were prepared by adding up to 30% TEC as a plasticizer and talc up to 200% as an antiadherent to a mixture of Eudragit RS 30D/RL 30D (95:5). The theophylline pellets were coated in a fluidized-bed coating unit and then cured at elevated temperatures. Theophylline pellets were successfully coated with the Eudragit dispersions that contained up to 200% talc, based on the dry polymer weight, and the coating efficiency was greater than 93%. Our results demonstrated that the polymer, which was plasticized by TEC, was able to function as a film-forming agent for dispersions containing high levels of talc. No sticking of the coated pellets was observed during the coating process or during the curing or equilibrating phase, even with high levels of TEC in the film. The dissolution rate of theophylline from the coated pellets was delayed when the film coating dispersion contained high levels of talc. Additionally, the stability of the drug release profiles from the coated pellets after storage was significantly improved. Furthermore, a modified dissolution testing used to simulate mechanical stresses that may be encountered in vivo showed the film coated pellets would have sufficient strength. The results of this study demonstrated that high levels of film additives in the acrylic dispersion contributed to the stabilization of the drug release rates as well as the reproducibility of the coating process.     

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.     

Effect of pectinolytic enzymes on the theophylline release from pellets coated with water insoluble polymers containing pectin HM or calcium pectinate

Theophylline pellets were coated with cellulosic (Aquacoat ECD 30, Surelease clear) or acrylic (Eudragit NE30D, RS30D) polymer aqueous dispersions, containing 10% (related to the insoluble polymer content) of pectin HM or calcium pectinate, using a Uni-Glatt fluidized-bed coating apparatus. When commercial pectinolytic enzymes were added to the dissolution media (0.05 M acetate - phosphate buffer, pH 6.0), the release of theophylline from the coated pellets was generally slower than that observed in the media without enzymes. The enzymatic slowing down of the drug release, depending on the type of the aqueous polymer dispersion used, is more important with mixed Eudragit NE/calcium pectinate coated pellets. The results obtained have been examined with regard to the validity of the approach based on the combination of pectins and the insoluble polymer aqueous dispersions intended for specific-delivery of drugs to the colon. The mechanism of the hydrophilic drug release from pellets coated with insoluble polymer aqueous dispersions containing an aqueous gel-forming polymer has been also discussed.     

Polymer Blends Used for the Coating of Multiparticulates: Comparison of Aqueous and Organic Coating Techniques

PURPOSE: The purpose of this study was to use polymer blends for the coating of pellets and to study the effects of the type of coating technique (aqueous vs. organic) on drug release. METHODS: Propranolol HCl-loaded pellets were coated with blends of a water-insoluble and an enteric polymer (ethyl cellulose and Eudragit L). Drug release from the pellets as well as the mechanical properties, water uptake, and dry weight loss behavior of thin polymeric films were determined in 0.1 M HCI and phosphate buffer, pH 7.4. RESULTS: Drug release strongly depended on the type of coating technique. Interestingly, not only the slope, but also the shape of the release curves was affected, indicating changes in the underlying drug release mechanisms. The observed effects could be explained by the higher mobility of the macromolecules in organic solutions compared to aqueous dispersions, resulting in higher degrees of polymer-polymer interpenetration and, thus, tougher and less permeable film coatings. The physicochemical properties of the latter were of major importance for the control of drug release, which was governed by diffusion through the intact polymeric films and/or water-filled cracks. CONCLUSIONS: The type of coating technique strongly affects the film microstructure and, thus, the release mechanism and rate from pellets coated with polymer blends.     

pH-independent release of a basic drug from pellets coated with the extended release polymer dispersion Kollicoat SR 30 D and the enteric polymer dispersion Kollicoat MAE 30 DP.

The objective of this study was to obtain pH-independent release profiles from coated pellets containing drugs with pH-dependent solubility. pH-independent release of the basic model drug verapamil HCl was achieved by coating with a combination of the neutral polymer dispersions Kollicoat SR 30 D (aqueous dispersion of polyvinyl acetate) and the enteric polymer dispersion Kollicoat MAE 30 DP (aqueous dispersion of methacrylic acid and ethyl acrylate copolymer; methacrylic acid copolymer type C). The two polymers where applied either as separate layers (enteric polymer + extended release polymer or vice versa) or as a polymer blend. A careful balance of the ratios of the polymers allowed the achievement of a pH-independent release. Higher amounts of the enteric polymer in the polymer blend resulted in a reversal of the pH-dependency, e.g. a faster release at pH 6.8 than in 0.1 N HCl.     

A burst drug release caused by imperfection of polymeric film-coated microparticles prepared by a fluidized bed coater

The aim of this study was to investigate the drug release from microparticles coated with various polymeric films. Ibuprofen-loaded microparticles with diameter of 250 and 300 microm were prepared by a fluidized bed granulator. Five polymers were used as coating materials, i.e., ethylene vinyl acetate, ethyl cellulose, ethyl cellulose aqueous dispersion, polyethacrylate or Eudragit NE 30D, and carnauba wax. The coating was performed with a fluidized bed coater. Afterwards the coated microparticles were characterized in terms of particle size, morphology, and drug content. The drug dissolution was also investigated in pH 7.4 phosphate buffer. In our attempts for production of extended release ibuprofen microparticles coated with polymeric films, it was shown that the coating process had a significant effect on drug release. The undesired burst release of ibuprofen was observed in all film-coated microparticulate formulations, resulting from the imperfection of coating films.     

盐酸罗沙替丁醋酸酯脉冲控释微丸的研制

目的:制备盐酸罗沙替丁脉冲控释微丸(ROXPCP)。方法:取空白丸芯分别以含药层、溶胀层(含交联羧甲基纤维素钠)和控释层(含乙基纤维素水分散体)顺序包衣制备ROXPCP,通过考察不同类型空白丸芯、溶胀层材料及溶胀层与控释层的不同包衣增重对药物释放的影响来优选工艺,并进行处方验证试验。结果:各考察因素均对药物的释放影响显著。优选工艺结果为:空白丸芯采用蔗糖型,溶胀层材料采用交联羧甲基纤维素钠,溶胀层和控释层包衣增重分别为15%、24%。以此制备的微丸时滞时间为4h左右,时滞后4h内累积释药百分率达到80%。结论:所制备的ROXPCP具有体外脉冲控释作用。     

Improved long term stability of aqueous ethylcellulose film coatings: importance of the type of drug and starter core

Instability during long term storage due to further gradual coalescence of the film remains one of the major challenges when using aqueous polymer dispersions for controlled release coatings. It has recently been shown that the addition of small amounts of poly(vinyl acetate)-poly(ethylene glycol)-graft-copolymer (PVA-PEG-graft-copolymer) to aqueous ethylcellulose dispersion provides long term stable drug release patterns even upon open storage under stress conditions in the case of theophylline matrix cores. However, the transferability of this approach to other types of drugs and starter cores exhibiting different osmotic activity is yet unknown. The aim of this study was to evaluate whether this novel approach is also applicable to freely water-soluble drugs and osmotically active sugar starter cores. Importantly, long term stable drug release profiles from coated diltiazem HCl-layered sugar cores could be achieved even upon open storage for 1 year under stress conditions (40 degrees C and 75% relative humidity). However, to provide desired drug release profiles the amount of added PVA-PEG-graft-copolymer must be adjusted. A minimal critical content of 10% (w/w) of this hydrophilic additive was identified, under which further polymer particle coalescence upon long term storage under stress conditions cannot be excluded. Potentially too rapid drug release can effectively be slowed down by increasing the coating level. Thus, adapting the polymer blend ratio and coating thickness desired and long term stable drug release profiles (even under stress conditions and open storage) can be provided for very different types of drugs and starter cores by the addition of small amounts of PVA-PEG-graft-copolymer to aqueous ethylcellulose dispersion.     

In Vitro Characterization of a Novel Polymeric System for Preparation of Amorphous Solid Drug Dispersions

Preparation of amorphous solid dispersions using polymers is a commonly used formulation strategy for enhancing the solubility of poorly water-soluble drugs. However, often a single polymer may not bring about a significant enhancement in solubility or amorphous stability of a poorly water-soluble drug. This study describes application of a unique and novel binary polymeric blend in preparation of solid dispersions. The objective of this study was to investigate amorphous solid dispersions of glipizide, a BCS class II model drug, in a binary polymeric system of polyvinyl acetate phthalate (PVAP) and hypromellose (hydroxypropyl methylcellulose, HPMC). The solid dispersions were prepared using two different solvent methods: rotary evaporation (rotavap) and fluid bed drug layering on sugar spheres. The performance and physical stability of the dispersions were evaluated with non-sink dissolution testing, powder X-ray diffraction (PXRD), and modulated differential scanning calorimetry (mDSC). PXRD analysis demonstrated an amorphous state for glipizide, and mDSC showed no evidence of phase separation. Non-sink dissolution testing in pH 7.5 phosphate buffer indicated more than twofold increase in apparent solubility of the drug with PVAP–HPMC system. The glipizide solid dispersions demonstrated a high glass transition temperature (T _g) and acceptable chemical and physical stability during the stability period irrespective of the manufacturing process. In conclusion, the polymeric blend of PVAP–HPMC offers a unique formulation approach for developing amorphous solid dispersions with the flexibility towards the use of these polymers in different ratios and combined quantities depending on drug properties.     

氟比洛芬乙基纤维素水分散体包衣小丸的制备及体外释药特性

目的：制备氟比洛芬包衣小丸，评价其体外释药特性。方法：离心造粒法制备空白丸芯及载药小丸；以乙基纤维素水分散体为包衣材料，羟阿基甲基纤维素为致孔剂，流化床制备氟比洛芬包衣小丸；释放度实验考察小丸的体外释药特性。结果：包衣小丸缓释胶囊的释放曲线与进口缓释胶囊ForbensR相似，羟丙基甲基纤维素的用量和介质pH值对释药影响显著，而热处理时间和胶囊壳对释药无显著性影响。结论：氟比洛芬包衣小丸具有较理想的体外缓释效果。     

Aqueous Ethylcellulose Dispersion of Ethylcellulose. I. Evaluation of Coating Process Variables

Formulation and process variables play an important role in the film-forming properties of coating polymers. Three selected independent coating process variables, namely, percent solids content in the coating polymeric dispersion, inlet-air temperature, and spray rate of the polymeric dispersion, were investigated in this study to determine their effect on the performance characteristics of tablets coated with a plasticized aqueous ethylcellulose dispersion (Surelease) in a fluid-bed equipment. Response surface methodology (RSM) was utilized to study the complex relationship between these process variables and selected response variables. Three response variables were considered, namely, rate of drug release from the untreated coated tablets and the thermal-treated coated tablets and microindentation hardness of the untreated coated tablets. A 12-point factorial experimental design was utilized, and three-dimensional (3-D) response surface plots were generated using a second-order polynomial model. The model provided information needed to predict optimal process conditions. Drug release from the coated tablets followed zero-order kinetics. Inlet-air temperature was found to be the most critical process variable for all the three response variables studied. A correlation was observed between the drug release rate and the microindentation hardness of the applied polymeric coat in the case of untreated coated tablets. The 3-D response surface plots indicated that lower rates of drug release from the coated tablets may be obtained by using high inlet-air temperature and low spray rate of the polymeric dispersion during coating.     

Different HPMC viscosity grades as coating agents for an oral time and/or site-controlled delivery system: a study on process parameters and in vitro performances

Currently, delayed/pulsatile release and colon delivery represent topics of remarkable interest. The present paper deals with the study and development of an oral dosage form devised to release drugs following a programmed time period after administration or, when opportune design modifications are introduced, to target the colon. The system is composed of a drug-containing core and a hydrophilic swellable polymeric coating capable of delaying drug release through slow interaction with aqueous fluids. An optional external gastroresistant film is applied to overcome gastric emptying variability, thus allowing colon delivery to be pursued according to the time-dependent approach. The aim of this work was to evaluate different hydroxypropyl methylcellulose (HPMC) viscosity grades as possible materials for the attainment of the system retarding hydrophilic layer. Both the relevant suitability for application onto tablet cores by aqueous spray-coating in fluid bed and capability of delaying drug release for a programmable period were explored and compared. Methocel E50 was found to afford the best balance among different important items, i.e. process time, retarding ability, dimensions of the coated units and possibility of finely tuning the delay duration. Further results pointed out the robustness of Methocel E50-based systems, which have shown to be practically unaffected by the concentration of the employed coating solution and the pH of the release medium, as well as only poorly influenced by ionic strength, at least with regard to values encompassed in the physiological range for gastrointestinal fluids.     

Evaluation of Drug-Containing Polymer Films Prepared from Aqueous Latexes

Polymeric films containing salicylic acid or propranolol HC1 were prepared by casting and drying a drug-containing, aqueous colloidal polymer dispersion (Eudragit NE 30D) as an alternative to films cast from organic polymer solutions. The drug was either dissolved (salicylic acid) or dissolved/ dispersed (propranolol HC1) in the polymeric matrix. Incompatibilities (flocculation or coagulation) between salts of basic drugs and two ethylcellulose latexes were overcome by substituting the anionic surfactants with a nonionic surfactant (Pluronic P103). The drug release was studied as a function of drug loading, film thickness, amount of hydrophilic additive (hydroxypropyl methylcellulose), and storage humidity. The release of propranolol HC1 (monolithic dispersion) was a combination of diffusion through the polymer and pores or channels; the extent of each release mechanism depended on the drug loading. On DSC thermograms, melting transitions were obtained with monolithic dispersions but not with monolithic solutions. The heat of fusion was linearly correlated to the amount of drug in the films. The amount of drug remaining in the film after the dissolution study was not detectable and corresponded to the drug dissolved in the polymer. The drug release increased with increased drug loading and increased amount of hydroxypropyl methylcellulose but was independent of film thickness and relatively insensitive to different storage humidities.     

结肠定位释药瓜尔胶/乙基纤维素包衣小丸

体外研究瓜尔胶/乙基纤维素混合包衣小丸的结肠靶向性。以5-氟尿嘧啶为模型药， 采用流化包衣技术以瓜尔胶/乙基纤维素混合物的水/醇混悬液对载药小丸进行喷液包衣。瓜尔胶/乙基纤维素混合包衣小丸的释药行为取决于包衣处方中瓜尔胶与乙基纤维素的比例和包衣厚度。分别以混合包衣液中瓜尔胶与乙基纤维素的比例及包衣增重为自变量， 以T₅和T₉₀（药物释放5%和90%所需要的时间）为效应， 进行3×4析因设计/效应面优化， 筛选较优处方。结果表明随着乙基纤维素在衣层中所占比例的增大及包衣厚度的增加， 药物释放时滞增加。当瓜尔胶与乙基纤维素的比例在0.2~0.7， 并且包衣增重在250%~500%时， T_5%为5.1～7.8 h， T_90%为9.8～16.3 h。并且在释药时滞之后， 进入模拟结肠微菌群酶解作用的释放环境中(pH 6.5)药物释放速度加快， T_90%缩短到9.0～14.5 h。由此可以看出适当的瓜尔胶/乙基纤维素混合衣层既可以保护药物顺利通过上消化道而不释放， 达到结肠后药物开始释放， 并且可在结肠微菌群的酶解作用下加速药物的释放， 实现结肠定位释药的目的。     

Evaluation of polyvinyl acetate dispersion as a sustained release polymer for tablets

Kollicoat SR 30D is a unique 30% aqueous dispersion of polyvinvyl acetate stabilized by polyvinyl-pyrrolidone intended for preparation of sustained release products. Detailed evaluation of this polymer dispersion as a sustained release coating for active pharmaceutical ingredients of two diverse classes of drugs was studied. A water insoluble drug (ibuprofen) and a water soluble drug (ascorbic acid) were selected as model active drugs. Ibuprofen was granulated using a GPCG-1 fluid bed processor prior to tableting, to improve the particle size and particle flow properties. In this process a 2(3) factorial design was implemented to evaluate the optimum process parameters such as spray rate, inlet air temperature and the inlet air velocity. The statistical model selected was Y(ijkl) = mu + tau(i) + beta(j) + theta(k) + (taubeta)ij + (betatheta)jk + (tautheta)ik + (taubetatheta)ijk + epsilon(ijkl). The factorial design showed that the spray rate, inlet air temperature, and inlet air velocity had a significant effect (p value <0.05) on the particle size. Significant improvement was observed in the flow properties of the granules. The granules were coated with Kollicoat SR30D dispersion using top spray method in the fluid bed processor. The dissolution studies showed that the release of ibuprofen decreased with an increase in the coating levels of Kollicoat SR 30 D. In the case of ascorbic acid, preparation of sustained release coated commercial granules was not possible due to the difficulty in coating a highly soluble drug particle. However, the coated granules when compressed into tablets showed some sustainability. Ibuprofen tablets manufactured with coated granules with a 15 g polymer for 300 g batch showed dissolution parameters of t50 and t90 at 4.2 hr and 7.5 hr, respectively. An approximate zero-type of release was observed when the polymer content was increased to 45 g for 300 g batch. Ascorbic acid tablets made with coated commercial granules having a total polymer content of 45 g per a 500 g batch showed an average dissolution t50 and t90 at 1.0 hr and 4.55 hr, respectively. When the total polymer content was increased to 60 g, per 500 g, the average dissolution t50 and t90 delayed to 1.40 hr and 7.20 hr, respectively.     

Eudraginated polymer blends: a potential oral controlled drug delivery system for theophylline

Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for micromeritic properties, drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl(?)) formulation. Asmanyl(?) tablets showed faster absorption (t(max) 4.0 h) compared to the TPH formulation showing a t(max) value of 8.0 h. The C(max) and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl(?), revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline.     

New levodopa sustained-release floating minitablets coated with insoluble acrylic polymer.

The aim of this study was to develop a new coated multiple-unit sustained-release floating system that is able to float over an extended period of time. Levodopa was used as a model drug. The system consisted of a 3mm drug-containing gas-generating core, prepared by melt granulation and subsequent compression, and coated with a flexible polymeric membrane. Eudragit RL30D and ATEC were used as a film former and a plasticizer, respectively. The coating level was fixed at 20% (w/w). The floating lag time decreased as the proportion of effervescent agents increased. The optimized coated floating minitablets could float within 20min and remained buoyant for more than 13h. In addition, a sustained release of levodopa for more than 20h was observed.