A mathematical model to predict the release of water-soluble drugs from HPMC matrices

A mathematical model to predict the fraction of water-soluble drug released as a function of release time (t, h), HPMC concentration (CH, w/w), and volume of drug molecule (V, nm3) was derived with ranitidine hydrochloride, diltiazem hydrochloride, and ribavirin as model drugs. The model is log (M(t)/M(infinity)) = 0.5 log t-0.3322CH-0.2222V-0.2988 (n = 140, r = 0.9848), where M(t) is the amount of drug released at time t, M(infinity) is the amount of drug released over a very long time, which corresponds in principle to the initial loading, n is the number of samples, and r is the correlation coefficient. The model was validated using isoniazid and satisfactory results were obtained. The model can be used to predict the release fraction of various soluble drugs from HPMC matrices having different polymer levels.     

The influence of excipients on drug release from hydroxypropyl methylcellulose matrices

The influence of commonly used excipients, spray-dried lactose (SDL), microcrystalline cellulose (MCC), and partially pregelatinized maize starch (Starch 1500) on drug release from hydroxypropyl methylcellulose (HPMC, hypromellose) matrix system has been investigated. A model formulation contained 30%w/w drug, 20%w/w HPMC, 0.5%w/w fumed silica, 0.25%w/w magnesium stearate, and 49.25%w/w filler. Chlorpheniramine maleate and theophylline were used as freely (1 in 4) and slightly (1 in 120) water-soluble drugs, respectively. It was found that for both drugs, addition of 20 to 49.25%w/w Starch 1500 resulted in a significant reduction in drug release rates compared to when MCC or SDL was used. The study showed that using lactose or microcrystalline cellulose in the formulations resulted in faster drug release profiles. Partially pregelatinized maize starch contributed to retardation of both soluble and slightly soluble drugs. This effect may be imparted through synergistic interactions between Starch 1500 and HPMC and the filler actively forming an integral part within the HPMC gel structure.     

Modified release from hydroxypropyl methylcellulose compression-coated tablets

The goal of this study was to obtain flexible extended drug release profiles (e.g., sigmoidal, pulsatile, increasing/decreasing release rates with time) with hydroxypropyl methylcellulose (HPMC) compression-coated tablets. Drugs of varying solubility (carbamazepine, acetaminophen, propranolol HCl and chlorpheniramine maleate) were incorporated into the tablet core in order to evaluate the flexibility/limitations of the compression-coated system. The HPMC-compression-coating resulted in release profiles with a distinct lag time followed by different release phases primarily determined by the drug solubility. Carbamazepine, a water-insoluble drug, was released in a pulsatile fashion after a lag time only after erosion of the HPMC compression-coat, while the more soluble drugs were released in a sigmoidal fashion by diffusion through the gel prior to erosion. With carbamazepine, increasing the molecular weight of HPMC significantly increased the lag time because of the erosion-based release mechanism, while, in contrast, molecular weight did not affect the release of the more soluble drugs. The lag-time and the release rate could also be well controlled by varying the HPMC amount in and the thickness of the compression-coating. A pulsatile release could also be achieved for water-soluble drugs by introducing an enteric polymer coating between the drug core and the HPMC compression-coating. This novel concept of introducing an enteric subcoating eliminated drug diffusion through the gelled HPMC layer prior to its erosion. Incorporating drug in the compression-coating in addition to the tablet core in varying ratios resulted in release profiles with increasing, decreasing or constant release rates. In conclusion, a versatile single-unit delivery system for a wide range of drugs with great flexibility in release profiles was presented.     

人工神经网络预测HPMC缓释片中易溶性药物的释放

目的应用BP人工神经网络模型预测水溶性药物从HPMC缓释片中的释放。方法以6种不同溶解性的水溶性药物(对乙酰氨基酚、氧氟沙星、盐酸环丙沙星、乳酸左氧氟沙星、多索茶碱、氯苯那敏、维拉帕米)为模型药物,设计62个处方,其中前面55个处方作为训练处方,另外7个处方作为验证处方,压制HPMC缓释片,进行释放度检查。以溶解度、载药量、HPMC的量、HPMC的固有黏度、MCC的量、PVP的浓度和药物溶出仪的转速作为自变量,药物在各个取样时间点的累积释放量作为输出,建立BP人工神经网络模型,并与响应面法进行对照,通过线性回归法和相似因子法比较人工神经网络和响应面法的预测能力,借助三维图说明各个变量对药物释放的影响。结果线性回归和相似因子法表明人工神经网络较响应面法的预测值与实际测定值更吻合,更能充分地说明单因素对药物释放的影响规律。结论人工神经网络可以代替响应面法处理HPMC缓释片处方设计中的不同溶解度的水溶性药物的多因素多响应的非线性问题而且可以推广到别的制剂设计中。     

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.     

Production of dosage forms for oral drug delivery by laminar extrusion of wet masses

Laminar extrusion of wet masses was studied as a novel technology for the production of dosage forms for oral drug delivery. Extrusion was carried out with a ram extruder. Formulations contained either microcrystalline cellulose (MCC) or dicalcium phosphate (DCP) as diluent, hydroxypropyl methylcellulose (HPMC), lactose, and water. Extrudates were characterized for their tensile strength, Young’s modulus of elasticity, water absorption, gel forming capacity, and release of two model drugs, coumarin (COU) and propranolol hydrochloride (PRO). Cohesive extrudates could be produced with both filling materials (MCC and DCP) when HPMC was included as a binder at low amounts (3.3–4.5% w/w dry weight). Employing more HPMC, the elasticity of the wet masses increased which resulted in distinct surface defects. For MCC, the maximum HPMC amount that could be included in the formulations (15% w/w dry weight) did not affect the mechanical properties or decrease the drug release significantly. For DCP extrudates, the maximally effective HPMC amount was 30% (w/w dry weight) with influence on both the mechanical properties and drug release. This study suggests that laminar extrusion of wet masses is a feasible technique for the production of dosage forms for oral drug delivery.     

Application of PVP/HPMC miscible blends with enhanced mucoadhesive properties for adjusting drug release in predictable pulsatile chronotherapeutics.

The aim of the present study was to prepare pulsatile release formulations consisting of two-layered tablets appropriate for preventing ischemic heart diseases. For this reason the active core was constituted by a FELO/PVP 10/90 w/w solid dispersion while for the adjustment of the drug release time the coating layer was composed of PVP/HPMC blends at different compositions, acting as a stimulus responsible layer. These blends as was found by DSC studies are miscible in the entire composition range, ensured by the interactions taking place between hydroxyl groups of HPMC and carbonyl groups of PVP. The miscibility of the system enhances the mucoadhesive properties of the blends, compared with those of pure HPMC, which is desired for such applications. The enhancement was attributed to the higher rate of wetting and flexibility of the new matrices due to the faster dissolution of the PVP macromolecules. Upon exposure of the prepared tablets to the release medium it was found that the coating layer disintegrates first, followed by the immediate release of FELO from the active core. The delaying time is based on a complicated mechanism, which is a combination of swelling and erosion of the PVP/HPMC polymer blends. Varying the PVP/HPMC blend ratios, the exact time that FELO is released during a daytime can be effectively adjusted and this ability is expressed mathematically by the equation t = 0.028 C1.5, where C is the concentration of HPMC in the blend.     

In-vitro and in-vivo evaluation of enteric-coated starch-based pellets prepared via extrusion/spheronisation

Pellet cores containing modified starch (high-amylose, crystalline and resistant starch) as the main excipient were enteric-coated with an Eudragit L30 D-55 based dispersion. The polymer weight gain was from 15% to 30% (w/w). Pellet cores were prepared using piroxicam (2.5% w/w, poor water solubility) and anhydrous theophylline (2.5% and 25% w/w, coarse and micronised powder, medium water solubility) as model drugs. Next to the water solubility, particle size and concentration of the model drugs, the influence of sorbitol (0% and 10%, w/w) and drying method (oven and fluid-bed) on pellet yield, size (Feret mean diameter), sphericity (aspect ratio, AR and two-dimensional shape factor, e(R)), friability, surface morphology and drug release were evaluated. Binder (HPMC) and granulation liquid (water) concentration were optimised to obtain maximum yield (size fraction between 900 and 1400 microm) and acceptable sphericity (AR<1.2). Pellet friability was <0.01% for all formulations, while the mean pellet diameter was lower for pellets with sorbitol and the ones dried in an oven. Mercury intrusion porosimetry combined with scanning electron microscopy revealed an influence of drying method and sorbitol level on the surface structure: the surface of fluid-bed dried pellets without sorbitol and with 2.5% of model drug was cracked, which correlated with a Hg-intrusion peak at the 6-80 microm pore size range. Due to improved mechanical properties of the wet mass, sorbitol addition smoothened the pellets as the main peak of Hg-intrusion shifted to a smaller pore size range. Using a higher drug concentration and micronised theophylline shifted the main peak of Hg-intrusion further towards the smaller pore size range. Oven-dried pellets showed no Hg-intrusion and no cracks were observed. When applying the highest coating thickness (30% weight gain), all theophylline pellet formulations were successfully coated (<10% drug release after 2h in acid dissolution medium), while pellets with the lowest coating thickness (15% weight gain) released from 5% to about 30% theophylline. The extent of drug release depended on the pellet composition and drying method as these factors determined the surface properties. Piroxicam release in acid medium was less than 1% irrespective of the surface characteristics, due to its poor water solubility. In basic medium (phosphate buffer, pH 6.8) all pellets released the drug in less than 45 min. The bioavailability of coated and uncoated piroxicam pellets was determined after oral administration to six dogs. Values of AUC(0-->72h), C(max) and t(max) after oral administration of piroxicam pellets to dogs were not significantly different from the values obtained for immediate release capsules (P>0.05).     

Calculation of the required size and shape of hydroxypropyl methylcellulose matrices to achieve desired drug release profiles

The aim of this study was to develop methods for the design of hydroxypropyl methylcellulose (HPMC) tablets with specified drug profiles. This was achieved by the use of a mathematical model developed to predict the release kinetics of water-soluble drugs from HPMC matrices. The required model parameters were determined experimentally for propranolol HCl and chlorpheniramine maleate in 0. 1 N HCl and phosphate buffer pH 7.4, respectively. Then, the effects of the dimensions and aspect ratio (radius/height) of the tablets on the drug release rate were evaluated. Independent experiments were conducted to verify the theoretical predictions. Acceptable agreement between theory and experiment was found, irrespective of the type of release medium and drug. However, statistical analysis revealed a structure in the resulting residuals. Drug release rates are overestimated at the beginning and underestimated at the end of the process. Possible explanations and modifications of the model are thoroughly discussed. Both, theoretical and experimental data showed that a broad spectrum of drug release patterns can be achieved by varying the size and shape of the tablet. The effect of the initial matrix radius on release was found to be more pronounced than the effect of the initial thickness. The practical benefit of the proposed method is to predict the required size and shape of new controlled drug delivery systems to achieve desired release profiles, thus significantly facilitating the development of new pharmaceutical products.     

The effect of polymer blends on release profiles of diclofenac sodium from matrices.

The purpose of this study was to evaluate the effect of polymer blends on the in vitro release profile of diclofenac sodium. Several controlled release matrices of diclofenac sodium with different proportions of hydroxypropyl methylcellulose (HPMC; viscosity grade 60 and 500 mPa.s), carbopol 940 and lactose as a water soluble filler were prepared. The results showed that when HPMC (viscosity grade 60 mPa.s) alone was used as matrix former, diclofenac sodium was released fast but the release rate became slower with HPMC (viscosity grade 500 mPa.s) at higher polymer/drug ratios (more than 0.8:1). However in lower polymer/drug ratios (lower than 0.7:1) the release rate still was fast. The results showed that carbopol can extend the release time appreciably but the release profiles had considerable fluctuations, and drug release in first hours was slow but increased appreciably with time at the end of profiles. When an appropriate blend of HPMC (viscosity grade 60 or 500 mPa.s) and carbopol 940 was used, the drug release became more uniform and its kinetic approached to zero order and release fluctuations were diminished. The results with these polymer blends showed that it is possible to reduce the total amounts of polymer in each formulation. According to kinetic analysis data, drug release from these matrix tablets did not follow Fick's law of diffusion and the results were in agreement with the earlier reports.     

Development of three layered buccal compact containing metoprolol tartrate by statistical optimization technique

The objective of this work to evaluate the effect of formulation variables on release properties and bioadhesive strength in development of three layered buccal compact containing highly water-soluble drug metoprolol tartrate (MT) by statistical optimization technique. Formulations were prepared based on rotatable central composite design with peripheral polymer ratio (carbopol 934P: HPMC 4KM) and core polymer ratio (HPMC 4KM: sodium alginate) as two independent formulation variables. The three layered buccal compact comprises a peripheral layer, core layer and backing layer. Four dependent (response) variables were considered: bioadhesion force, percentage MT release at 8 h, T50% (time taken to release 50% of drug) and release exponent (n). The release profile data was subjected to curve fitting analysis for describing the release mechanism of MT from three layered buccal compact. The main effects and interaction terms was quantitatively evaluated by quadratic model. The decrease in MT release was observed with an increase in both the formulation variables and as the carbopol: HPMC ratio increases the bioadhesive strength also increases. The desirability function was used to optimize the response variables, each having a different target and the observed responses were highly agreed with experimental values. The results demonstrate the feasibility of the model in the development of three layered buccal compact containing highly water-soluble drug MT.     

Effect of hydroxypropylmethylcellulose (HPMC) on the release profiles and bioavailability of a poorly water-soluble drug from tablets prepared using macrogol and HPMC

The aim of the present study was to investigate the effect of hydroxypropylmethylcellulose (HPMC-2208), used as an excipient for controlled release of drug, on the release profiles and bioavailability of the poorly water-soluble nifedipine (NP) from a tablet prepared using macrogol 6000 (PEG) and HPMC. The crushing tolerance of the NP tablet prepared using PEG and HPMC (NP-PEG-HPMC tablet) was markedly increased with increasing compression force used during the preparation from 20 to 200 MPa. The values reached their maximal levels (approximately 13 kg for the NP-PEG-HPMC tablet and 8 kg for the PEG tablet) at the compression force of 100 MPa. Although NP is a poorly water-soluble drug, it was rapidly dissolved from the NP-PEG tablet (without HPMC) due to the improvement of its dissolution rate in the presence of PEG. NP dissolution was complete at the latest within 1 h. On the other hand, dissolution of NP from the NP-PEG-HPMC tablet was significantly delayed with an increase in the concentration of HPMC in the tablet. The dissolution of NP from the NP-PEG-HPMC tablet containing 50% HPMC-2208 was markedly delayed as the viscosity of HPMC also increased. Interestingly, the same peak plasma NP concentration (C(max)) and the area under the plasma NP concentration-time curve (AUC(0-10)) were observed for both the NP-PEG tablet and NP-PEG-HPMC tablets, however, the time to C(max) (t(max)) for the NP-PEG-HPMC tablet was significantly higher when the NP-PEG-HPMC tablet was orally administered to rabbits. We describe here a preparation method of a new sustained-release NP-PEG-HPMC tablet using a mixture of NP-PEG granules (prepared with PEG) and HPMC.     

吲哚拉辛HPMC骨架片药物释放因素研究

目的 考察影响吲哚拉辛亲水性骨架片体外释药的各种因素。方法 以羟丙基甲基纤维素（HPMC）为骨架材料,用湿法制粒和粉末直接压片法制备缓释骨架片,并考察HPMC用量、粒度、制备方法、片子大小及其它辅料对吲哚拉辛HPMC骨架片的体外释药的影响。结果 吲哚拉辛HPMC骨架片的体外释药均符合Higuchi方程。HPMC的用量,粒度和制法,片子大小对吲哚拉辛的释放速率随HPMC粒度和片子的减小而减慢。淀粉、PVP、MCC的加入（每片HPMC的含量不变）均加快吲哚拉辛释药速率,且加入量不同,其释药速率问具有显著性差异。随着EC加入量的增加（≥40mg。片^-1）．吲哚拉辛释放速率显著加快。结论 HPMC用量和粒度、制备方法、片子大小及其它辅料为影响吲哚拉辛骨架片释放速率主要因素。     

羟丙基甲基纤维素的性质对药物亲水性骨架片溶出度的影响

考察了羟丙基甲基纤维素(HPMC)的羟丙基含量、HPMC颗粒大小和HPMC的粘度对模型药物卡托普利、扑尔敏和蚓哚美辛(消炎痛)骨架片药物溶出的作用。结果表明药物溶解度不同对骨架片中HPMC不同性质的影响也不同。HPMC羟丙基含量增高,溶出速率加快;而卡托普利和扑尔敏则相反。HPMC颗粒大小对卡托普利和扑尔敏骨架片溶出影响较小,但对蚓跺美辛骨架片有一定影响,表现为HPMC颗粒越小,溶出速率越慢。由HPMCK100构制的骨架片对3种药物均达不到阻滞释放的作用。HPMCK4M,K15M和K100M的粘度差异对卡托普利和扑尔敏的溶出影响不大,但随着粘度增加吲跺美辛的溶出速率减慢。     

Asymmetric membrane capsules for delivery of poorly water-soluble drugs by osmotic effects

A non-disintegrating polymeric capsule system, in which asymmetric membrane offers an improved osmotic effect, was used to deliver poorly water-soluble drugs in a control manner. The capsule wall membrane was made by a phase inversion process, in which asymmetric membrane was formed on stainless-steel mold pins by dipping the mold pins into a coating solution containing a polymeric material followed by dipping into a quench solution. This study evaluates the influence of coating formulation that was cellulose acetate (CA), ethylcellulose (EC), and plasticizer (glycerin and triethyl citrate). Results show capsule that made by CA with glycerin (formulation A), which appear in asymmetric structure and are able to release chlorpheniramine maleate (CM) in significant percentage. Two poorly water-soluble drugs of felodipine (FL) and nifedipine (NF) were selected as the model drug to demonstrate how the controlled release characteristics can be manipulated by the design of polymeric capsules with an asymmetric membrane and core formulations. Results show that sodium lauryl sulfate (SLS) is able to promote the release of FL from polymeric capsules prepared with CA with asymmetrical membrane. The addition of solubilizer, including RH40, PVP K-17, and PEG 4000 could enhance the release of FL but with an extent not being related to its solubility. Based on these results, influence of core formulation variables, including the viscosity and added amount of hydroxypropyl methylcellulose (HPMC), the added amount of SLS, and drug loading were examined on the release of NF. It was found that HPMC of 50 cps was suitable to be a thickening agent and both added amount of HPMC and SLS showed a comparable and profoundly positive effect, whereas NF loading had no influence on the drug release percent and rate. There existed a synergistic interaction between HPMC and SLS on the release percent and rate.     

Novel design of osmotic chitosan capsules characterized by asymmetric membrane structure for in situ formation of delivery orifice

In this study, chitosan capsules with asymmetric membrane to induce osmotic effects and in situ formation of the delivery orifice were optimally prepared and characterized. Chitosan capsules were formed on stainless steel mold pins by dipping the pins into a chitosan solution followed by forming asymmetric structure by dipping into a quenching solution containing tripolyphosphate (TPP) to cause an ionic cross-linking reaction between the outer layer of chitosan and TPP. Factors influencing the properties of the capsule membrane, such as the molecular weight of chitosan, the dipping solution and dipping time, and the quenching solution and time, were optimized to successfully produce osmotic chitosan capsules with asymmetric membrane using chitosans that possessed different viscosities. In situ formation of a delivery orifice on the asymmetric membrane of the chitosan capsule was proven by the observation of a jet stream of chlorophyll being released from the capsule. Drugs with different solubility were selected, and a linear correlation between drug solubility and the initial drug release rate calculated from the slope of the drug release profile was used to verify that the delivery orifices that were in situ formed on the asymmetric membrane of the chitosan capsules induced by osmotic effect was responsible for the drug release. Water permeability across the optimally produced asymmetric membrane of the capsule from chitosan of 500 cps (300-700 cps) quenched with TPP for 30 min (C500/TPP30) was determined to be 1.40 x 10(-6)cm(2)h(-1)atm(-1) at 37.0+/-0.5 degrees C. The encapsulation of poorly water-soluble drugs, felodipine (FE) and nifedipine (NF), in such an asymmetric chitosan capsule was capable of creating a sufficient osmotic effect to activate the release of the drug with the addition of SLS and HPMC. The multiple regression equations of maximal release percent at 24h for FE and NF confirmed that both sodium lauryl sulfate (SLS) and hydroxypropyl methylcellulose (HPMC) positively influenced this response factor, and the effect of SLS was greater than that of HPMC.     

Controlled-release matrix tablets of ibuprofen using cellulose ethers and carrageenans: effect of formulation factors on dissolution rates.

The study was conducted to investigate the effects of carrageenans, and cellulose ethers on the drug release rates of ibuprofen controlled-release tablet matrices prepared by direct compression. Polymer blends containing carrageenans or cellulose ethers were used for the formulation and the effect of varying the polymer concentration on the release of the drug was studied. Other factors such as changes in surface topography of the matrices due to hydration were observed using a cryogenic scanning electron microscopy technique. Multiple regression analysis was used to predict the time for 50% release (t50) as a function of the concentration of the polymers used. Most of the formulations showed linear release profiles (r(2)>or=0.96-0.99) and sustained the release of ibuprofen over 12-16 h. The highest t50 (9.3 h) was for the formulation that contained a blend of 1:2 ratio of Viscarin and HPMC, while the lowest (3 h) was for the matrices that contained a 2:1 ratio of methylcellulose and Gelcarin. The majority of the matrix tablets that contained 10% polymer disintegrated prematurely. Of all the polymer blends that were investigated, the combination of Viscarin and HPMC gave almost linear release profiles over the entire range of concentration that was studied. The least effective combination was methylcellulose in combination with HPMC. Most of the formulations released ibuprofen by an anomalous (non-Fickian) transport mechanism, except those matrices that contained methylcellulose and Gelcarin (in a 1:1 and 1:2 ratio), which showed zero-order release.     

Hildebrand solubility parameter to predict drug release from hydroxypropyl methylcellulose gels

An equation including the Hildebrand solubility parameter δ of the drugs is used for the first time to model drug release from hydroxypropyl methylcellulose (HPMC) gels: l nM = -21.578 + 2.102 δ-0.037 δ(2)+0.48 ln t + 1.028 ln C(i) (r(2) = 0.94 for a total of 286 cases). The experimentally determined release data of six drugs having different polarity (caffeine, theophylline, paracetamol, salicylic acid, naproxen and diclofenac) at several initial concentrations C(i) were included in the equation. In general, the amount of drug delivered is linear at the first 5-6h of the release profiles and the zero order constants K(o) increase as the solubility parameter of the drugs become larger. The Peppas exponential law M/M(∞) = Kt(n) is applicable to larger fractional release, until 67-87% (48-51 h) for the less polar drugs (diclofenac and naproxen, lower δ values) and more than 80% (26-28 h) for the more polar drugs (higher δ values, theophylline, salicylic acid, caffeine and paracetamol). The Peppas release rate (lnK) shows a parabolic relationship with the drug solubility parameter. The diffusional exponent n varies between 0.40 and 0.58 indicating that drug release is mainly controlled by diffusion. An extended form of the Peppas equation is also tested for each drug including all the initial concentrations: lnM = a + b ln t + c ln C(i) (r(2) = 0.88-0.94). The logarithm of the octanol-water partition coefficients can also be used in combination with the drug concentrations.     

Influence of water soluble additives and HPMCP on drug release from sureleaseê-coated pellets containing tamsulosin hydrochloride

The objective of this study was to investigate the influence of various water-soluble additives and HPMCP as an enteric polymer into Surelease for the developement of oral controlled release system containg tamsulosin hydrochloride. The drug loaded pellets were coated with only Surelease or Surelease containing HPMC, PEG 4000, mannitol and HPMCP (20% w/w). In case of HPMC and PEG 4000 as additives into Surelease film, the rapid drug release was observed in pH 1.2 while the higher drug release was achieved by adding HPMCP into Surelease as well as by increasing the amount of HPMCP (10, 20, and 30% w/w) in pH 7.2. The incorporation of HPMCP into Surelease showed pH-denpendent drug release due to its pH-dependent nature. Therefore, the incorporation of HPMCP into Surelease based on aqueous coating formulation is an effective way to develop oral controlled release delivery systems containing tamsulosin hydrochloride.     

Formulation of biphasic release tablets containing slightly soluble drugs.

A new biphasic release system for slightly soluble drugs has been proposed. To enhance the dissolution rate, the drug was milled with a superdisintegrant. Then, double-layer tablets were prepared. One layer was formulated to release the drug in a very short time (fast-release). The other consisted of an extended-release hydroxypropylmethylcellulose (HPMC) matrix. Different HPMC concentrations (10, 16 and 22%) and viscosity grades (Methocel K4, K15 and K100M) were used to obtain different release rates of the drug from the extended-release layer, ketoprofen and praziquantel were used as slightly soluble model drugs.The in vitro dissolution tests of the prepared double-layer systems, showed the desired biphasic behaviour: the drug contained in the fast releasing layer dissolved within the first 15 min, while the drug contained in the prolonged-release layer was released at different times, depending on the formulation of the hydrophilic matrix. In particular, an increase in the percentage and viscosity grade of HPMC, in the extended release layer, leads to a decrease in the drug delivery rate and produces a wide range of different release rates from only a few hours up to 24 h.