In vivo release of testosterone from protein-vinyl polymer composites

Hydrophilic vinyl polymer-protein composites containing testosterone were made by means of thermal denaturation of albumin after radiation-induced polymerization of 2-hydroxyethylmethacrylate (HEMA) at −78°C. The albumin-HEMA mixed polymer can be considerably digested with trypsin. The degree of digestion was smaller than that expected from calculation. It was deduced that the digestion of the albumin component was retarded in the presence of HEMA. The same tendency was observed in in vivo experiments. At the same time, in vivo release of testosterone was depressed in albumin-HEMA mixed polymer composite in accordance with the weight decrease of polymer composite resulting from digestion. The effect of testosterone on the weight of ventral prostate was investigated using composites in castrated Wistar rats. The effect was larger in the controlled slow release from implanted composites rather than that of dosage by injection. The microscopic observation showed that the inflammation and foreign body reaction in rat tissue were retarded in albumin-HEMA mixture polymer composite compared with 100% albumin composite.     

Biodegradable random copolypeptides of β-benzyl L-aspartate and γ-methyl L-glutamate for the controlled release of testosterone

The random copolypeptides of β-benzyl L -aspartate (β-Bz L -Asp) and γ-methyl L -glutamate (γ-Me L -Glu) were synthesized and implanted subcutaneously in rats. It was found that the resulting copolypeptides are degraded and also have good biocompatibility in vivo. On the basis of these results, poly(β-Bz L -Asp-co-γ-Me L -Glu) was tried to be used as a material for a drug delivery system. Copolypeptide-testosterone composites were prepared at a pressure of 200 kg/cm² in the presence of a slight amount of dichloroethane. The in vivo release rate of testosterone from copolypeptide-drug composites was about 5,5 times higher than that in vitro. The in vivo release rate remained relatively constant over a period of 90 days at 0,22 mg/day. The serum testosterone concentration in castrated rats was 0,40 ng/ml and the value went up to 6,8 ng/ml after the biodegradable copolypeptide-testosterone composite was implanted and was kept constant for the duration of test.     

Studies on biodegradation and release of gentamicin sulphate from interpenetrating network hydrogels based on poly(acrylic acid) and gelatin: in vitro and in vivo

Interpenetrating network hydrogels (IPNs) based on poly(acrylic acid) and gelatin (Ge) were evaluated for in vitro and in vivo biodegradation and in vivo release of gentamicin sulphate. In vitro and in vivo degradation studies demonstrated that with the increase of acrylic acid content in the polymer, the rate of degradation decreases, and a reverse phenomenon was observed with increasing Ge content in the hydrogel. The rate of in vivo degradation was much lower than in vitro degradation. Incorporation of gentamicin sulphate in hydrogel further reduces their degradation. In vitro and in vivo drug release profile showed a burst effect, followed by controlled release. Drug concentration was measured in the local skin tissue, blood serum, kidney, liver and spleen. The local skin tissue concentration of 50% and 100% gentamicin sulphate, loaded full IPNs (i.e., Ax-1 and Ax-2), was found to be higher (20+/-2mug/g) than the minimum bactericidal concentration for Staphylococcus aureus (1.2mug/g) and Pseudomonas aeruginosa (10mug/g), respectively, for a study time of 60 days.     

Testosterone metabolism by the prostate of the aging AXC rat

Testosterone metabolism by the ventral prostate of inbred, senescent (36-month-old) AXC rats showed a shift to increased oxidative and diminished reductive metabolism when compared to young mature (3-month-old) or mature adult (6-month-old) AXC rats. The change was principally attributable to diminished production of 5α-dihydrotestosterone and increased production of 4-androstenedione. By contrast, dorsolateral prostate testosterone metabolism in these same rats was always more reductive than that of ventral prostate and failed to show the post-maturation shift to oxidative testosterone metabolism which characterized ventral prostate. Co-incubation of either ventral or dorsolateral prostate from any of these rats with testosterone and estradiol showed that estradiol did not significantly affect prostate testosterone metabolism. Plasma testosterone content of senescent AXC rats was only 28% of that of mature adult rats. Chronic exogenous testosterone treatment enhanced reductive testosterone metabolism by ventral prostate and eliminated those changes in metabolite distribution which had differentiated testosterone metabolism by young and senescent AXC rats. The data support the interpretation that the aging-related diminution in AXC rat ventral prostate reductive metabolic capacity is primarily the consequence of diminished 5α-dihydrotestosterone production secondary to diminished plasma testosterone content.     

In vitro and in vivo kinetics of regulated drug release from polymer matrices by oscillating magnetic fields

The kinetics of drug release from polymer-drug matrices containing an embedded magnet was continuously monitored in vitro and in vivo. The application of an oscillating magnetic field increased the rate of drug release from the polymer matrices. Within the limits of detection the increase in release occurred immediately, remained stable for as long as the field was applied, and returned exactly to baseline upon withdrawal of the field. The increase in release was directly proportional to field amplitude. The same pattern of results were observed in vivo as in vitro, though higher strength fields were required in vivo to achieve the same effect observed in vitro.     

Pneumadin in the ventral prostate of rats during postnatal development: a radioimmunological and immunocytochemical study

We have recently demonstrated that the ventral prostate of adult rats contains high levels of pneumadin (PNM), a decapeptide originally isolated from mammalian lung, and that testosterone is needed for the maintenance of a normal level of the peptide in the prostate. Hence, we have investigated, by radioimmunoassay (RIA) and light ultrastructural immunocytochemistry (ICC), PNM concentration and localization in the rat ventral prostate during postnatal development. RIA showed that PNM content increased steadily from day 20 to day 90 of postnatal life, parallel to the increase in the prostate weight. In contrast, PNM concentration remained rather stable, although it showed a marked rise at day 40 when rat testes are known to reach their full maturation. ICC demonstrated that PNM immunoreactivity was mainly located in the apical pole of epithelial cells of rat ventral prostate, especially in the subcellular organelles involved in protein secretion, i.e. rough endoplasmic reticulum cisternae, vacuoles and granules. Taken together our study suggests the involvement of PNM in the functional control of rat prostate during postnatal maturation, although its exact role remains to be elucidated.     

Control of cilostazol release kinetics and direction from a stent using a reservoir-based design

Sustained release formulations of a potent antithrombotic drug, cilostazol, in poly-(lactic acid-co-glycolic acid) (PLGA) matrices were created for luminal release from a novel drug-eluting stent utilizing reservoirs (RES TECHNOLOGY?). The crystallinity of cilostazol and the morphology of the cilostazol/polymer matrix in the stent reservoirs were examined by cross-polarized optical microscopy and differential scanning calorimetry. An in vitro method was developed to study release kinetics of various cilostazol formulations and to examine correlation with in vivo release. Formulation parameters such as drug-to-polymer ratio and the use of a polymer barrier on the abluminal surface of the drug/polymer matrix were found to be effective in modulating drug release rate. Cilostazol/PLGA(75/25) in the weight ratio of 50/50 to 70/30 displayed first-order release kinetics for the majority of the drug load. Addition of an abluminal polymer barrier slowed cilostazol release rate when compared to the bidirectional reservoir design. Excellent correlation between cilostazol in vivo release profile from stents in a porcine coronary artery model and that measured in vitro in a modified USP-7 apparatus suggests that the in vitro release system is capable of predicting in vivo release of cilostazol from stent reservoirs.     

Effect of dexamethasone and testosterone treatment on the regulation of insulin-degrading enzyme and cellular changes in ventral rat prostate after castration

Insulin-degrading enzyme (IDE) has been shown to enhance the binding of androgen and glucocorticoid receptors to DNA in the nuclear compartment. Glucocorticoids cause hyperglycaemia, peripheral resistance to insulin and compensatory hyperinsulinaemia. The aim of the present study was to investigate the effect of dexamethasone (D), testosterone (T) and dexamethasone plus testosterone (D + T) on the regulation of IDE and on the remodelling of rat ventral prostate after castration (C). Castration led to a marked reduction in prostate weight (PW). Body weight was significantly decreased in the castrated animals treated with dexamethasone, and the relative PW was 2.6-fold (±0.2) higher in the D group, 2.8-fold (±0.3) higher in the T group and 6.6-fold (±0.6) higher in the D + T group in comparison with the castrated rats. Ultrastructural alterations in the ventral prostate in response to androgen deprivation were restored after testosterone and dexamethasone plus testosterone treatments and partially restored with dexamethasone alone. The nuclear IDE protein level indicated a 4.3-fold (±0.4) increase in castrated rats treated with D + T when compared with castration alone. Whole-cell IDE protein levels increased approximately 1.5-fold (±0.1), 1.5-fold (±0.1) and 2.9-fold (±0.2) in the D, T and D + T groups, respectively, when compared with castration alone. In conclusion, the present study reports that dexamethasone-induced hyperinsulinaemic condition plus exogenous testosterone treatment leads to synergistic effects of insulin and testosterone in the prostatic growth and in the amount of IDE in the nucleus and whole epithelial cell.     

Studies of the slow releasing of testosterone from radiation-polymerized testicular prostheses implanted subcutaneously in the back of castrated rabbits

A controlled release testicular prosthesis containing testosterone, which was previously dissolved in 2-hydroxyethyl methacrylate (HEMA) at a temperature of 80 degrees C, was prepared by radiation-induced polymerization in the supercooled state at a low temperature. The daily dose of testosterone released in vitro from the poly(HEMA) testicular prosthesis was kept constant at a rate of 5.5 +/- 1.5 mg/d throughout an experimental period of 900 d. In the in vivo experiments, the poly(HEMA) testicular prosthesis was implanted subcutaneously in the back of castrated rabbits over a maximum period of 11 mnth. The cumulative amounts of testosterone released in vitro and in vivo from the poly(HEMA) testicular prosthesis for a period of 11 mnth were found to be 2.1 g (30.0 wt% of initial drug) and 0.9 g (12.8 wt% of initial drug), respectively. The serum testosterone level in castrated rabbits with a poly(HEMA) testicular prosthesis rapidly decreased for periods up to 2 mnth (after increasing during the first 2 wk), then showed a moderate decrease for a few months, and finally held constant at a level of 10 ng/ml throughout the experimental period. It was concluded that a slight amount of testosterone is continuously released in vivo from the radiation-polymerized poly(HEMA) testicular prosthesis over a long period analogous with that in vitro.     

Development of rat prostatitis model by oral administration of isoflavone and its characteristics

Inflammation of the prostate can be induced experimentally in rats by the subcutaneous administration of estrogen. However, it is usually achieved at the price of some alteration in the sex steroid hormone balance and morphological changes in the prostate. In this study, a soy-extracted isoflavone mixture with weak estrogenic activity was administered orally in an attempt to induce prostatitis in a more physiologic way and to characterize the inflammation induced. A total of 36 male Sprague-Dawley rats, 8 weeks old, were divided into 2 groups. The control group was fed with only an AIN-76A diet containing no detectable phytoestrogen and the experimental group was fed with AIN-76A and a soy- extracted isoflavone mixture (genistein 60.0% and daidzein 19.6%), 300 mg/kg body weight for 9 weeks. The sequential body weight and prostate weight at necropsy were measured. A histologic examination and histomorphometry assessed the changes in the prostate. The serum concentrations of testosterone and dihydrotestosterone were measured to estimate the effects on the androgen level. Intraprostatic concentrations of genistein and daidzein were measured by gas chromatography/ mass spectroscopy (GC/MS). While no sign of prostate inflammation was apparent in the control group, severe inflammatory changes in the stroma, increased epithelial detachment and inflammatory exudates within the glandular lumen of the dorsolateral prostate were observed in more than 80%(15/18) of the experimental group. However, there was no significant difference in the ventral prostate between the two groups. The daidzein and genistein concentrations in both the lateral and ventral prostates were significantly higher in the experimental group than in the control group where no isoflavone was detectable. In addition, the concentrations were much higher in the dorsolateral than in the ventral prostate. Although the body weight gain was not consistent in the experimental group, there were no significant differences in the prostate weight and serum androgen level between groups. In summary, when a soy-extracted genistein and daidzein-rich isoflavone mixture was administered orally into rats, prostatic inflammation with characteristic lobe specificity developed. The present method of inducing prostatitis seems to be a more physiologic than an estrogen-induced experimental model, and sequential pharmacokinetic studies might help in establishing this model as a more valuable tool in assisting future research in this field.     

Preparation, characterization, and release behavior of aspirin-loaded poly(2-hydroxyethyl acrylate)/silica hydrogels

Poly(2-hydroxyethyl acrylate) (PHEA) is a polymer hydrogel that can be used as a biomaterial. In this study, PHEA/silica composites containing aspirin as a model drug were prepared, and their drug release behaviors were tested. 2-Hydroxyethyl acrylate (HEA) was first copolymerized with 3-(trimethoxysilyl) propyl methacrylate (MSMA) in the presence of ammonium persulphate and then condensed with silicic acid oligomer. The composites were characterized with Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). In addition, water uptake and matrix erosion of PHEA/silica of different weight ratios were also investigated. The results indicated that the silica particles were well dispersed in PHEA hydrogels. The in vitro drug release test revealed that the release rate of aspirin decreased with the increasing content of silica. The drug release behaviors were analyzed by employing the power law, which showed that the release profiles were governed either by Case II diffusion or by anomalous diffusion. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay of rabbit chondrocytes revealed that adding silica can improve the biocompatibility of PHEA to some extent.     

Degradation behaviour in vitro for poly(D,L-lactide-co-glycolide) as drug carrier

Biodegradable polymers have been extensively investigated because of regulating drug release rate easily, obviating the need to remove the device, and good biocompatibility. Among the biodegradable polymers currently under investigation, poly(D,L-lactide-co-glycolide) (PLGA) copolymers are the most widely studied because of their long history of safe clinical use as drug carrier. 50 : 50 PLGA was used as a model degradable polymer in this study to investigate the degradation behaviour on drug release from bulk degradable polymers in vitro. 5-fluorouracil (5-FU) was used as a model drug. Molecular weight change, residual mass, water uptake, morphological change of PLGA wafers, and pH of release test medium were characterized to investigate the effect of polymer degradation on drug release. The release rate of 5-FU increased with the increase of 5-FU loading amount and the release profiles of 5-FU irrespective of 5-FU loading amount followed near first order release kinetics.     

Experimental diabetes has adverse effects on the differentiation of ventral prostate during sexual maturation of rats

Diabetes mellitus of both type I (insulin-dependent) and type II (noninsulin-dependent) has adverse effects on male sexual and reproductive functions in adolescent boys and men, which include impairment of spermatogenesis, reduced sperm count, serum testosterone and seminal fluid volume, impotency, and loss of libido. Streptozotocin (STZ)-induced diabetes in rats provides a relevant model to study reproductive dysfunction under diabetic conditions, as they exhibit a number of deficits in reproductive function that resemble those seen in human diabetics. Therefore, the present investigation is aimed to understand the effects of STZ diabetes on the structure and development of ventral prostate during the critical period of sexual maturation in rats. Prepubertal (40-days-old) male Wistar rats were made diabetic by single injection of STZ (120 mg/kg body weight, intraperitoneally). Induction of diabetes was confirmed by serum insulin titer, hyperglycemia, and polyuria. To another set of STZ-diabetic rats, after 3 days of diabetes induction, insulin was replaced at a dose of 3 U/100 g body weight, subcutaneously in two equally divided doses at 8:00 AM and 6:00 PM. Diabetes caused regression of prostate, leading to a decrease in the absolute weight. Histologically, glandular epithelium has undergone shrinkage with transformation of acinar cells into low cuboidal type with less prominent secretory granules and blebs. Nevertheless, the secretory activity was not totally abolished. Interstitial space was increased due to shrinkage of glandular epithelium. Histomorphometric studies on the tubular diameter, volume and surface density of acinar epithelium, lumen, and stroma also support regressive changes in prostate. Insulin replacement prevented the detrimental effects of diabetes partially. These findings implicate the adverse effects of STZ diabetes on the differentiation of ventral prostate during sexual maturation.     

Oral exposure to methylmercury modifies the prostatic microenvironment in adult rats

Methylmercury (MeHg) is an environmental pollutant that is highly toxic to the central nervous system. As its effects on male reproductive system are poorly understood, this study was carried out to analyse the effects of MeHg on the rat prostate. To evaluate the MeHg toxicity on ventral prostate, three groups of adult male Wistar rats received oral doses of 0.5, 1.0 and 3.0 mg/kg MeHg, respectively, on a daily basis for 14 days. A fourth group was used as a control. The prostate weight was decreased in rats treated orally with 0.5 mg/kg MeHg compared to controls. Also, Hg concentration increased significantly in the prostate after treatments. There were reductions in serum testosterone levels and androgen receptor immunoreactivity in animals receiving 3.0 mg MeHg/kg. The stereological data showed changes in the prostatic epithelial, stromal and luminal compartments which varied according to the different doses. Histopathological alterations, such as chronic inflammation, stratified epithelial hyperplasia and epithelial inflammatory reactive atypia, were observed in the 0.5 mg/kg MeHg‐treated group. Epithelial atrophy was observed in the 3.0 mg/kg MeHg‐treated group. In conclusion, the MeHg affects prostatic homoeostasis resulting in histopathological changes that may be relevant in the pathogenesis of prostatic disease.     

Immunofluorescent localization of an androgen-dependent isoenzyme of prostatic acid phosphatase in rat ventral prostate

Isoenzymes of rat ventral prostate (RVP) acid phosphatase were isolated and partially purified by ultracentrifugation, Sephadex G-100 column chromatography, and isoelectric focusing. Antisera were raised to the isoenzymes of prostatic acid phosphatase by immunization of New Zealand white rabbits. Rabbit antisera reacting specifically to homologous but not heterologous isoenzymes of acid phosphatase were then reacted with a variety of tissues using indirect immunofluorescence. The tissues included prostate, spleen, bone marrow, liver, kidney, salivary gland complex, small intestine, and adrenal glands. An antiserum against a RVP acid phosphatase isoenzyme with a pI of 4.5 (A-PAP) localized acid phosphatase only in the supranuclear region of rat ventral prostate epithelial cells, and did not react with acid phosphatase in any of the other organs tested. A-PAP did not localize acid phosphatase in the ventral prostate from rats 14 days after castration. A-PAP did localize acid phosphatase in the ventral prostate from castrated animals that were treated with testosterone. These results indicate the A-PAP localized an androgen-dependent isoenzyme of acid phosphatase in RVP epithelial cells that may be secretory in nature. This antiserum should prove to be an ideal marker for studies involving hormonal regulation of prostatic epithelial function in vivo and in vitro.     

Hydroxyapatite/poly(epsilon-caprolactone) composite coatings on hydroxyapatite porous bone scaffold for drug delivery

Hydroxyapatite (HA) porous scaffold was coated with HA and polycaprolactone (PCL) composites, and antibiotic drug tetracycline hydrochloride was entrapped within the coating layer. The HA scaffold obtained by a polymeric reticulate method, possessed high porosity ( approximately 87%) and controlled pore size (150-200 microm). Such a well-developed porous structure facilitated usage in a drug delivery system due to its high surface area and blood circulation efficiency. The PCL polymer, as a coating component, was used to improve the brittleness and low strength of the HA scaffold, as well to effectively entrap the drug. To improve the osteoconductivity and bioactivity of the coating layer, HA powder was hybridized with PCL solution to make the HA-PCL composite coating. With alteration in the coating concentration and HA/PCL ratio, the morphology, mechanical properties, and biodegradation behavior were investigated. Increasing the concentration rendered the stems thicker and some pores to be clogged; as well increasing the HA/PCL ratio made the coating surface be rough due to the large amount of HA particles. However, for all concentrations and compositions, uniform coatings were formed, i.e., with the HA particles being dispersed homogeneously in the PCL sheet. With the composite coating, the mechanical properties, such as compressive strength and elastic modulus were improved by several orders of magnitude. These improvements were more significant with thicker coatings, while little difference was observed with the HA/PCL ratio. The in vitro biodegradation of the composite coatings in the phosphate buffered saline solution increased linearly with incubation time and the rate differed with the coating concentration and the HA/PCL ratio; the higher concentration and HA amount caused the increased biodegradation. At short period (<2 h), about 20-30% drug was released especially due to free drug at the coating surface. However, the release rate was sustained for prolonged periods and was highly dependent on the degree of coating dissolution, suggesting the possibility of a controlled drug release in the porous scaffold with HA+PCL coating.     

In vitro and in vivo degradation of poly(D, L-lactide-co-glycolide)/amorphous calcium phosphate copolymer coated on metal stents

The purpose of this study was to optimize a novel biodegradable polymer for drug eluting stent (DES) applications. Degradation profiles of different poly(D,L-lactide-co-glycolide)/amorphous calcium phosphate (PLGA/ACP) composites coated on stents were studied both in vitro and in vivo for three months. For the in vitro study, stents were immersed into the phosphate buffered saline (37 °C, pH 7.4) with constant shaking. The polymer weight loss was measured weekly and morphological changes were analyzed. The results demonstrated that approximately 60% of polymer was degraded within the three-month period and there was no significant difference between the different PLGA/ACP composites. However, the composite of 50% PLGA (65/35) with 50% ACP showed a slightly faster degradation rate than other composites. Morphologically, all stent surfaces changed from a micro-porous before degradation to a corrugated solid micro-net-like structure at two months post degradation. Based on in vitro results, 65% PLGA (65/35) with 35% ACP) coated stents were selected and implanted into rat aortas (n = 12) for the in vivo study. Microscopic observation showed that no composite was found on any of the implanted stents at 12 weeks post implantation, which indicated the selected PLGA/ACP composite is desired for DES applications.     

Testosterone action on the ventral prostate lobe of the castrated rat as assessed with a stereologic morphometric method

The effects of testosterone (1 mg testosterone propionate/100 g body weight for 30 days) on the ventral prostates of rats castrated 30 days prior to the onset of hormone treatment was investigated with a stereologic morphometric method. Testosterone induced rapid growth of the prostate, which was reflected by a 29-fold increase in acinar parenchyma but only a 2.6-fold increase in interacinar tissue. There was a 23-fold increase in the total amount of glandular epithelium and a 36-fold increase in total luminal amount. Various volumetric fractions, total surface area, total tubule length, height of the epithelium, mean diameter of the tubules, and mean distance between the tubules and between the glandular centers were calculated. Growth of the acinar parenchyma, especially of the glandular lumen, was the dominant pattern. We could not demonstrate any remarkable responses in the interacinar tissue during any phase of testosterone treatment.     

Natural killer (NK) cell cytotoxicity in athymic (nude) rats

The in vitro and in vivo natural killer (NK) cell activity of congenitally athymic, nude (ATH) rats and of normal, euthymic (EUTH) rats was compared. We found: a) a higher level of in vitro NK cell activity in blood, spleen and lymph nodes of ATH rats compared with their heterozygous littermates, b) in the spleen the number of NK lytic units per organ was not higher in ATH compared with EUTH whereas it was significantly higher in lymph nodes, c) a lack of age-dependence of in vitro NK cell activity tested in culture with heat inactivated fetal calf serum, d) a higher rate of in vivo elimination of target tumor cells in 4-week ATH rats compared with EUTH rats, e) an age-dependent decrease in the rate of in vivo target cell elimination in both groups, and finally, f) an age-dependent increase in the inhibitory effect of autologous serum on NK cell activity in vitro in both groups. These findings show that the blood and lymphoid organs of athymic rats contain a substantially higher proportion of NK cells, active both in vitro and in vivo against K562 tumor cells, than their euthymic littermates. In the spleen this increased proportion can be attributed to the lack of T cells, whereas in the ATH rat lymph nodes there is an absolute increase in NK cell activity, and that the decrease of cytotoxicity in vivo with age reflects the increasing inhibitory properties of autologous serum both in nude and in normal rats.     

Formulation and characterization of modified release tablets containing isoniazid using swellable polymers

The aim of this work was to develop swellable modified release (MR) isoniazid tablets using different combinations of polyvinyl acetate (PVAc) and sodium-carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation technique and then compressed into tablets. In vitro release studies for 12 hr were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Tablets of all formulations were found to be of good physical quality with respect to appearance (width and thickness), content uniformity, hardness, weight variation and friability. In vitro release data showed that increasing total polymer content resulted in more retarding effect. Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12(th) hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that this combination can be used to formulate zero order release tablets of water soluble drugs like isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian transport is the primary mechanism of isoniazid release from PVAc and Na-CMC based tablets. The value of mean dissolution time decreased with the increase in the release rate of drug clearly showing the retarding behavior of the swellable polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may be feasible to formulate zero order release tablets of water soluble drugs like isoniazid.