Sustained release of acetaminophen from a heterogeneous mixture of two hydrophilic non-ionic cellulose ether polymers

This study examined the release of acetaminophen (APAP) from hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) matrices. The effect of pseudoephedrine (PE) as a co-active, HPMC:HPC ratio, polymer loading, pH of the dissolution media, and compression force on APAP release were studied. Granules formulated with APAP or both APAP and PE, and various blends of HPMC and HPC were compressed into tablets at different compression forces. APAP release from the matrix tablets was not considerably influenced by changes in HPMC:HPC ratio or compression force. The rate of drug release was significantly affected by pH of the dissolution media, total polymer loading, and the presence of PE. Drug release from the formulations containing both APAP and PE was slower than those containing only APAP. Drug release from tablets formulated with APAP only showed an initial burst at pH 1.16 or 7.45. Formulations containing both APAP and PE showed slower drug release at pH 1.16 than at pH 7.4. The drug release data showed a good fit to the Power Law Model. The mechanism of drug release is consistent with a complex behavior. The results of the tablet erosion studies indicated that the amount of APAP released was linearly related to the percentage of tablet weight loss. The kinetics of tablet water uptake was consistent with a diffusion and stress relaxation mechanism.     

Studies on vaginal bioadhesive tablets of acyclovir

Bioadhesive vaginal tablets were prepared using poly(acrylic acid) (PAA); Methylcellulose (MC), carboxymethyl cellulose (CMC), hydroxypropyl cellulose (HPC) and hydroxypropylmethyl cellulose (HPMC) as bioadhesive polymers in different concentrations and acyclovir as drug by direct compression technique (DCT) and wet granulation technique (WGT). Physical tests were applied to the tablets. The swelling behavior of vaginal tablets in distilled water, lactic solution and cow vagina, acyclovir release rate in lactic solution and bioadhesion to vaginal mucosa in cow vagina, in situ, were investigated. Swelling of the tablets containing HPC, CMC and MC was very rapid and caused disintegration of the tablets. The swelling behaviour of the tablets containing HPMC lasted 6 h in lactic solution. The force (N) necessary to detach the tablets from the vaginal tissue was found to depend on concentration and type of the bioadhesive polymer. The tablets containing HPMC needed the most detachment force.     

The effect of formulation composition and dissolution parameters on the gel strength of controlled release hydrogel tablets.

The impact of hydrogel polymers and dissolution media on tablet gel strength, Gamma, of controlled release (CR) hydrogel tablets was investigated. CR tablets containing either hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), or carbomer were formulated with theophylline and Fast Flo lactose, to produce tablets with a polymer content of 8, 15, and 30% w/w. Gamma was measured using a previously reported method. The drug dissolution profiles were similar, irrespective of polymer type or dissolution media (DI water, 0.1 N HCl, and pH 6.8 phosphate buffer), at the same % w/w level of polymer. Gamma, however, showed large and significant differences (p < or = 0.05) between tablets containing different polymers and between different dissolution media. Gamma values were HPMC KI00MP > HPC HXF > carbomer 971P (same % w/w) with absolute Gamma values at 30% w/w in DI water of 6600, 4600, and 1600 ergs/cm3, respectively. Gamma for HPMC based tablets was independent of changes in dissolution media, while the Gamma values for HPC tablets were 18% lower in acid and buffer than in DI water. Of the polymers tested, carbomer based tablets had the lowest Gamma values in all dissolution media and an unexpected 58% lower Gamma in buffer compared with DI water or acid. Gamma provides a quantitative measure of the effect of formulation and dissolution parameter changes on tablet gel layer strength, under in vitro stress conditions that may parallel in vivo tablet performance, but which cannot be deduced from a comparison of dissolution profiles or polymer viscosity.     

Understanding and Managing the Impact of HPMC Variability on Drug Release from Controlled Release Formulations

The purpose of this study is to identify critical physicochemical properties of hydroxypropyl methylcellulose (HPMC) that impact the dissolution of a controlled release tablet and develop a strategy to mitigate the HPMC lot-to-lot and vendor-to-vendor variability. A screening experiment was performed to evaluate the impacts of methoxy/hydroxypropyl substitutions, and viscosity on drug release. The chemical diversity of HPMC was explored by nuclear magnetic resonance (NMR), and the erosion rate of HPMC was investigated using various dissolution apparatuses. Statistical evaluation suggested that the hydroxypropyl content was the primary factor impacting the drug release. However, the statistical model prediction was not robust. NMR experiments suggested the existence of structural diversity of HPMC between lots and more significantly between vendors. Review of drug release from hydrophilic matrices indicated that erosion is a key aspect for both poorly soluble and soluble drugs. An erosion rate method was then developed, which enabled the establishment of a robust model and a meaningful HPMC specification. The study revealed that the overall substitution level is not the unique parameter that dictates its release-controlling properties. Fundamental principles of polymer chemistry and dissolution mechanisms are important in the development and manufacturing of hydrophilic matrices with consistent dissolution performance. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1664–1672, 2014     

The effect of controlled release tablet performance and hydrogel strength on in vitro/in vivo correlation

The impact of controlled release (CR) formulations having different gel strength values (gamma) on in vivo tablet performance and the in vitro/in vivo correlation of the formulations was investigated. The CR tablets containing either hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), or carbomer were formulated with theophylline and Fast Flo lactose to produce tablets with a polymer content of 8 and 30% w/w. gamma was measured using a previously reported method. Male beagle dogs were utilized. Results showed that dissolution profiles were similar for all three polymers at the same % w/w level of polymer, irrespective of media (DI H2O, 0.1 N HCl, and pH 6.8 phosphate buffer). Mean gamma values were significantly different (p < or = 0.05) and were in order of HPMC K100MP > HPC HXF > carbomer 971P (same 30% w/w) with absolute gamma values at 30% w/w in DI H2O of 6600, 4600, and 1600 ergs/cm3, respectively. Drug profiles in plasma for the 30% HPMC K100MP tablets were consistent with in vitro dissolution profiles and gamma values. Plasma profiles for the 30% HPC HXF tablets were similar in vivo as the HPMC tablets. Plasma profiles for the 30% carbomer 971P formulation showed much higher drug concentrations (compared to HPMC and HPC) in vivo in all dogs. This findings is not consistent with the slow drug release found in the dissolution profiles but consistent with its low in vitro gamma values. Assessment of the predictability of a level A in vitro/in vivo correlation was quantified by absolute mean percent prediction error (PE). Formulations having gamma approximately 6000 ergs/cm3 have acceptable PE < 20%, and low standard deviation (sigma). Results showed that gamma values of CR hydrogel tablets in vitro will affect the in vivo performance (i.e., absorption kinetics of the drug) of the tablets and were also found to better assess (compared to in vitro dissolution profiles alone) the predictability of in vitro/in vivo correlations (level A and multiple level C).     

Effect of penetration enhancers on the release and skin permeation of bupranolol from reservoir-type transdermal delivery systems

A reservoir-type transdermal delivery system (TDS) of bupranolol (BPL) was designed and evaluated for different formulation variables like gel reservoirs (made with anionic and nonionic polymers), rate controlling membranes and penetration enhancers on the drug release and in vitro skin permeation kinetics of the devices. Keshary-Chien type diffusion cells and pH 7.4 phosphate buffered saline (PBS) were used for drug release studies and excised rat skin was used as a barrier for permeation experiments. The release rate of BPL from nonionic polymer gel reservoirs [hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC)] was much higher than anionic polymer gel reservoirs [carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (Na CMC) and sodium alginate)]. Among different rate controlling membranes, Cotran-polyethylene microporous membrane demonstrated highest release rate for BPL than all other membranes. An optimized TDS formulation with HPC gel and Cotran-polyethylene microporous membrane was used to study the effect of penetration enhancers on the release and skin permeation rate of BPL from the TDS. Permeation rates of the devices containing 5% (w/v) pyrrolidone (PY) or 1-methyl-2-pyrrolidone (MPY) were about 3- and 1.5-fold higher than control (no enhancer, P<0.01) indicating PY to be better penetration enhancer for BPL than MPY. The permeation rates of devices containing partially methylated beta-cyclodextrin (PMbetaCD) and PMbetaCD-BPL complex were about 2.5- and 1.4-fold higher than control (P<0.01). Inclusion of 10 and 30% w/v propylene glycol (PG) in the devices increased the permeation rate by 1.4- and 1.8-fold higher than control (P<0.05). In conclusion, reservoir-type TDS of BPL was developed and penetration enhancers increased the skin permeation of BPL at 4-5 times higher levels than the desired target delivery rate.     

Formulation and physicochemical characterisation of buccoadhesive films containing ketorolac

Ketorolac tromethamine, the non-steroidal anti-inflammatory drug, was formulated onto buccoadhesive films to overcome the limitations in the currently available dosage and routes of administration which in sequence will increase patients’ compliance. Films were cast from organic and aqueous solvents using various bioadhesive polymers namely: sodium carboxymethyl cellulose (Na-CMC), hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC) and Carbopol 934. The prepared films were subjected to investigations for their physical and mechanical properties, swelling behaviors, in vitro bioadhesion, drug permeation via bovine buccal mucosa and in vitro drug release. These properties were found to vary significantly depending on the preparation methods, the type of the polymers and the ratio of addition of both plasticizer (i.e. polyethylene glycol) and film forming agent (ethyl cellulose and polyvinylpyrolidene). Formula number K10 containing carbopol 0.5% and HPMC 0.5% was found to be the best film as it shows good adhesion, acceptable pH, and gives a reasonable ketrolac release (about 85-90% at 6 h). In addition, this film was subjected to in vitro and in vivo release. The obtained results indicate that the concentration of ketorolac in the oral cavity was maintained above 4.0 μg/mL for a period of at least 6 h. This film shows promising results for using the ketrolac buccoadhesive route of administration topically and systemically, and thus it will be subjected to clinical evaluation in future work.     

Aqueous ethyl cellulose dispersion containing plasticizers of different water solubility and hydroxypropyl methyl-cellulose as coating material for diffusion pellets II: properties of sprayed films.

This study investigates the properties of sprayed films prepared from aqueous ethyl cellulose dispersions (ECD) containing hydroxypropyl methylcellulose (HPMC) and plasticizers of different water solubility in order to clarify the drug release mechanisms of pellets coated with the respective material. It is of special interest to measure the migration of the water soluble components as well as the physical properties of the swollen ethyl cellulose film. Swelling experiments with sprayed films in 0.1 N-HCl at 37 degrees C show that fairly water soluble plasticizers and the pore forming agent (HPMC) migrated rapidly and almost completely out of the films. The water insoluble plasticizers remain predominantly in the film and the migration rate of HPMC is reduced in a release medium of high ionic strength. The glass transition temperature (T(g)) and the softening temperature (T(s)) of these films after swelling are dependent on the water solubility of the plasticizer. The T(g) of ECD films plasticized with triethyl citrate is above the swelling temperature of 37 degrees C after migration of the plasticizer, transforming the polymer in the glassy state. In contrast, dibutyl phthalate-containing ECD films demonstrate a T(g) below the swelling temperature, leaving the polymer in the rubbery state. The mechanical properties of dry and wet films are studied as a function of the state of curing of the films and of the swelling temperature. On contact with water, a pronounced shrinkage of ECD/HPMC films plasticized with water insoluble plasticizers is observed. All these results are used to explain the different drug release mechanisms of the coated pellets and to enable the prediction and optimization of drug release-rates from coated pellets.     

Comparative evaluation of rate of hydration and matrix erosion of HEC and HPC and study of drug release from their matrices.

Hydrophilic polymers, in contact with the dissolution medium, may swell and make a continuous gel layer, erode or undergo combination of the two. The swelling action of these polymers is controlled by the rate of their hydration in the dissolution medium. The extent of polymer swelling, relative mobilities of dissolution medium and drug, and matrix erosion dictate the kinetics as well as mechanism of drug release from the polymeric matrices. The objective of the present investigations was to study the rate of hydration and the rate of matrix erosion of two hydrophilic, non-ionic cellulose ethers, i.e., hydroxyethylcellulose (HEC) and hydroxypropylcellulose (HPC), and to compare the kinetics and mechanism of drug release from their matrices. Chlorpheniramine maleate was used as the model drug. Matrix tablets containing chlorpheniramine maleate, HEC or HPC and dicalcium phosphate were compressed at 156 MPa pressure. The rate of hydration of the polymer, rate of erosion of the matrices and in vitro drug release studies were carried out in phosphate buffer (pH 7.4). The hydration studies of the two polymers demonstrated that due to relatively larger water uptake, the degree of swelling of HEC matrices was considerably higher as compared to the HPC matrices. Also, HEC matrices exhibited relatively higher erosion as compared to HPC matrices. The drug release from HEC matrices occurred by non-Fickian transport, i.e., combination of drug diffusion and polymer swelling, while drug release from HPC matrices was controlled primarily by diffusion through pores and channels in the structure. The t(50%), time to reach 50% drug release, for HEC matrices was 4.8 h and that for HPC matrices was 6.5 h which indicates that a higher polymer level was needed in the case of HEC matrices to sustain the drug release for up to 12 h of dissolution as compared to HPC matrices due to relatively higher hydrophilicity of HEC.     

Oral controlled release formulations of rifampicin. Part II: Effect of formulation variables and process parameters on in vitro release

Hydrophilic controlled release matrix tablets of rifampicin, a poorly soluble drug, have been formulated using hydroxypropyl methylcellulose (HPMC) polymer (low, medium, and high viscosity) by direct compression method. Influence of formulation variables and process parameters such as drug:HPMC ratio, viscosity grade of HPMC, drug particle size, and compression force on the formulation characters and drug release has been studied. Our results indicated that the release rate of the drug and the mechanism of release from the HPMC matrices are mainly controlled by the drug:HPMC ratio and viscosity grade of the HPMC. In general, decrease in the drug particle size decreased the drug release. Lower viscosity HPMC polymer was found to be more sensitive to the effect of compression force than the higher viscosity. The formulations were found to be stable and reproducible.     

Compaction properties, drug release kinetics and fronts movement studies of matrices combining mixtures of swellable and inert polymers. III: effect of polymer substitution type

Theophylline radial release from cellulose derivatives with different substitution type (HPMC K4M, HPC H, MC A4M) matrix tablets has been modulated by the introduction of a new inert polymeric excipient, at different proportions (75, 50, 25%). The new polymer was hydroxypropylcellulose-methyl methacrylate (HCMMA), which was dried either in a vacuum oven (OD-HCMMA) or freeze-dried (FD-HCMMA). MC A4M and its mixtures presented the best compaction properties results, especially mixed with FD-HCMMA, according to 100% mixtures. Only high levels of HCMMA (75%) in the matrices showed interesting differences to drug release modulation. Also, at this proportion (75:25), the HPC H mixtures presented the highest differences in relation with OD or FD HCMMA respect to the other cellulose polymers. HPMC K4M and HPC H mixtures showed a combination of diffusion and erosion release mechanisms. The last one was nearly negligible in MC A4M mixtures, according with its highest diffusion rate constant values, and the absence of hydroxypropyl substituents. Only HPMC K4M mixtures presented a diffusion front that moves outwards, while HPC H and MC A4M moves inwards. The modulation of theophylline radial release was obtained using a high percentage of HCMMA, and the use of two cellulosic ethers, one of them with just one type of substituent (MC A4M or HPC H) and the other with two types of substituent (HPMC K4M). Another possibility is changing the HCMMA copolymer (OD or FD) in the 75/25 mixture with HPC.     

Analysis of surface properties of cellulose ethers and drug release from their matrix tablets.

Detailed knowledge based on new developments, especially in analytical techniques, is needed for characterizing polymer excipients. Inverse gas chromatography (IGC) is a useful method for investigating polymer surfaces in terms of thermodynamic parameters. The aim of our work was to study the correlation between polymer surface properties determined with IGC and the mechanisms of release of water-soluble pentoxifylline and vancomycin hydrochloride from cellulose ether matrices. Tablets were made of hydroxypropyl (HPC), hydroxyethyl (HEC) or hydroxypropylmethyl (HPMC) cellulose and contained 25% of drug. Differences in dispersive component of the surface free energy for these polymers were relatively small and ranged from 26 to 33mN/m. However, polar properties, expressed as specific component of the enthalpy of adsorption and as acid-base properties show larger differences between the polymers and demonstrate their relative polarity in the order HEC>HPMC>HPC, which correlates well with water sorption on bulky polymers and with the swelling degree of polymer matrices. The release of pentoxifylline and vancomycin from HPC is governed mainly by Fickian diffusion, whereas from HEC the relaxation of polymer chains is important too. The analysis of the release profiles in the light of Peppas-Sahlin model lead to the conclusion that the surface properties of the cellulose ethers influence the interactions with water and the release mechanisms of the drug. It was found out, that data obtained by IGC enable rapid inference about the behaviour of polymers in water and the release of water-soluble drugs.     

A novel ketoconazole bioadhesive effervescent tablet for vaginal delivery: design, in vitro and 'in vivo' evaluation

Bioadhesive tablet formulations of ketoconazole for vaginal delivery were studied. Carbomer (Carbopol 974P, Carbopol 934P), hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) were used as candidate bioadhesive polymers. Effervescent was incorporated into the formulations as a disintegration agent. The swelling behavior and bioadhesive strength of the drug-free tablets were investigated. Carbopol 934P was selected as biopolymer in combination with HPMC or HPC at different ratios to develop five drug-loaded formulations. The swellings, tackiness and in vitro release were studied on the tablets. A good sustained effect and a moderate bioadhesion were obtained with the tablets. The formulation containing 100 mg of effervescent, with the Carbopol 934P:HPC ratio of 1:9, seemed to be the optimum one for the tablet. In vivo drug residence tests were carried out by administering the preferred formulation to female rats. The results showed that the drug remaining followed a one-order model. Even after 24 h of administration in vagina of rats, 17% of the original employed drug was retained on the vaginal tissue. Our study may provide a potential vaginal tablet formulation of ketoconazole against Candida albicans.     

Drug release behavior of polymeric matrix filled in capsule

A single unit sustainable drug release system was developed using hydroxypropyl methylcellulose (HPMC)-based matrices filled in capsule as the drug delivery device. Release behavior of propranolol HCl from these capsules was investigated and least square fitting was performed for the dissolution data with the different mathematical expressions. Effect of diluent, polymer, pH and hydrodynamic force on the drug release from the developed systems was investigated. The utilization of HPMC as a matrix former extended the drug release longer than 8 h. HPMC viscosity grades affected the drug release, that is, increasing the amount of fillers such as lactose and dibasic calcium phosphate enhanced the drug release rate of HPMC matrices. The hydrodynamic force, type and amount of incorporated polymer apparently influenced the drug release. The physiochemical properties of polymers and interaction between HPMC and other polymers were important factors for prolongation of the drug release. The release mechanism from HPMC-based matrices in capsules was the non-Fickian transport in which the sustainable drug release of HPMC capsules could be achieved by the addition of polymeric matrix.     

Sustained Release of Acetaminophen from Heterogeneous Matrix Tablets: Influence of Polymer Ratio,Polymer Loading,and Co-active on Drug Release

ABSTRACT

The aim of this research was to investigate the effect of pseudoephedrine (PE), polymer ratio, and polymer loading on the release of acetaminophen (APAP) from hydroxypropyl methyl cellulose (HPMC)/polyvinylpyrrolidone (PVP) matrices. Granules formulated with APAP or both APAP and PE, and various blends of HPMC and PVP were compressed into tablets at varying compression forces ranging from 2000 to 6000 lb. In vitro drug release from the matrix tablets was determined and the results correlated with those of tablet water uptake and erosion studies. Drug release from the formulations containing both APAP and PE was slower than those containing only APAP (P < 0.05, F = 3.10). Drug release from tablets formulated with APAP only showed an initial burst at pH 1.16 or 7.45, and at high total polymer loading (≥ 9.6%). Formulations containing both APAP and PE showed slower drug release at pH 1.16 than at pH 7.45. At pH 1.16, a decline in the percentage of APAP released occurred after 18 hours. This was due to the hydrolysis of APAP to p-aminophenol. The drug dissolution data showed good fit to the Korsmeyer and Peppas model, and the values of the release exponents ranged from 0.20 to 0.62, indicating a complex drug release pattern. Tablet erosion studies indicated that the amount of APAP released was linearly related to the percentage of tablet weight loss. The kinetics of tablet water uptake was consistent with a diffusion and stress relaxation controlled mechanism. Overall, the results of this study indicated that PE, as a co-active in the formulation, modified the matrix, and hence retarded APAP release.     

Tablets of paliperidone using compression-coated technology for controlled ascending release

The aim of this work was to prepare ascending release compression-coated (CC) tablets with paliperidone (PAL) using a simple manufacturing technique and short manufacturing process. The release behavior and mechanisms in vitro of the final tablets was investigated and evaluated. The PAL CC tablets were comprised of a core layer of high viscosity hydroxypropyl cellulose (HPC-H) and a coating layer of high viscosity hydroxypropyl methylcellulose (HPMC-K100M). Several factors such as materials and core tablet compositions were studied for their influence in the formulation procedure. The drug release mechanism was studied using gravimetric analysis. The data could be fitted to the Peppas model. The ascending drug release results were expressed in terms of the slope of the release curve at different time points. Results showed that the formulation could achieve a good ascending drug release when the weight ratio of PAL was 5:1 (core:layer). The fraction of HPC and HPMC was 33 %, and the combination of Eudragit RL-PO was 10%. The ascending release mechanism was due to solvent penetration into the PAL CC tablets, and subsequent drug dissolution from the gelatinous HPC and HPMC matrix erosion. The release mechanism was therefore a combination of diffusion and erosion. This work demonstrated that the compression-coated tablets could achieve controlled ascending release over 24 h for the oral administration systems.     

Release of theophylline and carbamazepine from matrix tablets - Consequences of HPMC chemical heterogeneity

The release of theophylline and carbamazepine from matrix tablets composed of microcrystalline cellulose, lactose and hydroxypropyl methylcellulose (HPMC) was studied. The aim was to investigate the effect of different substituent heterogeneities of HPMC on the drug release from matrix tablets composed of either 35% or 45% HPMC. The release of the poorly soluble carbamazepine was considerably affected by the HPMC heterogeneity, and the time difference at 80% drug release was more than 12 h between the formulations of different HPMC batches. This was explained by slower polymer erosion of the heterogeneous HPMC and the fact that carbamazepine was mainly released by erosion. In addition, results from magnetic resonance imaging showed that the rate of water transport into the tablets was similar. This explained the comparable results of the release of the sparingly soluble theophylline from the two formulations even though the polymer erosion and the swelling of the tablets were considerably different. Thus, it can be concluded that the drug release was highly affected by the substituent heterogeneity, especially in the case of carbamazepine, which was released mainly by erosion.     

A novel approach to sustained pseudoephedrine release: differentially coated mini-tablets in HPMC capsules

We developed and optimized a novel pseudoephedrine hydrochloride (PSE) sustained-release dosage form. The system comprises immediate-release mini-tablets (IRMT) and sustained-release mini-tablets (SRMT) contained in a hydroxypropyl methylcellulose (HPMC) capsule. The IRMT contained PSE, excipients and low-substituted hydroxypropyl cellulose (a disintegrant), and the tablets were coated with HPMC, a water-soluble polymer. IRMT prepared with varying amounts of low-substituted hydroxypropyl cellulose all dissolved completely within the first 60min, so low-substituted hydroxypropyl cellulose content does not greatly influence PSE release. The SRMT contained only PSE and excipients, and were coated with a mixture of HPMC and the water-insoluble polymer ethylcellulose. The PSE release profile for the SRMT could be controlled by varying the thickness of the coat, and the lag time could be controlled by varying the amount of ethylcellulose present in the polymer coat. PSE was released immediately from our encapsulated mini-tablet system and release was sustained over an extended period of time: the PSE in the IRMT dissolved within 60min, whereas the PSE in the SRMT was released over 8-10h. This system can be modified to yield various extended drug-release profiles, thereby harnessing the benefits of both SRMT and IRMT.     

Mixture design of theophylline retard formulation

Three different cellulose derivatives (hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC) and microcrystalline cellulose (MC)) were used to prepare tablets containing 10% of theophylline with the aid of wet granulation. The retardation effect of different compositions of these cellulose derivatives was investigated. Using mixture design, the formulations with the best retardation properties were selected. On the basis of these results, tablets with different compositions containing 60% (300 mg) of theophylline were prepared. The simulation was performed on a personal computer with the implemented digital simulation language SIMCOS to predict steady-state plasma levels. It was established that formulation C, composed of 34.6% of MC 4.7% of HPMC 0.7% of HPC and 60% of theophylline exhibits in vivo the same retardation effect as commercially available theophylline tablets.     

Effect of various surfactants and their concentration on controlled release of captopril from polymeric matrices

Various methods are available to formulate water soluble drugs into sustained release dosage forms by retarding the dissolution rate. One of the methods used to control drug release and thereby prolong therapeutic activity is to use hydrophilic and lipophilic polymers. In this study, the effects of various polymers such as hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC) and sodium carboxymethylcellulose (CMC) and surfactants (sodium lauryl sulphate, cetyltrimethylammonium bromide and Arlacel 60) on the release rate of captopril were investigated. The results showed that an increase in the amount of HPMC K15M resulted in reduction of the release rate of captopril from these matrices. When HPMC was partly replaced by NaCMC (the ratio of HPMC/NaCMC was 5:1), the release rate of the drug significantly decreased. However, there was no significant difference in release rate of captopril from matrices produced with ratios of 5:1 and 2:1 of HPMC/NaCMC. The presence of lactose in matrices containing HPMC and NaCMC increased the release rate of captopril. It was interesting to note that although partial replacement of HPMC by EC reduced the release rate of the drug (ratio of HPMC/EC 2:1), the release rate was increased when the ratio of HPMC/EC was reduced to 1:1. The effects of various surfactants on the release rate of captopril from HPMC/EC (1:1) matrices were also investigated. The results showed that the surfactants did not significantly change the release rate of the drug. Release data were examined kinetically and the ideal kinetic models were estimated for the drug release. The kinetic analysis of drug release data from various formulations showed that incorporation of surfactants in HPMC/EC matrices did not produce a zero-order release pattern.