Crystal engineering of valproic acid and carbamazepine to improve hygroscopicity and dissolution profile.

Sodium valproate, the most common solid form of valproic acid, is highly hygroscopic and carbamazepine has extremely low aqueous solubility. Producing a salt form of valproic acid with tromethamine and a cocrystal form of valproic acid with carbamazepine have been studied as two approaches to improve physicochemical properties of the intended drugs. Characterization methods including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR) are applied to characterize the synthesized salt and cocrystal. The stability of sodium valproate and tromethamine valproate were examined in 33, 53, 75 and 100 percent of relative humidity. The dissolution profile studies were performed in phosphate buffer media (pH = 6.8) for carbamazepine (a low soluble drug) and carbamazepine-valprocic acid cocrystal. Tromethamine valproate was physically more stable than sodium valproate in exposure to humidity. Carbamazepine-valproic acid cocrystal did not show an extreme improvement in dissolution profile when compared with carbamazepine, however after 24 hcocrystal was more soluble.

Physicochemical and in vitro mucoadhesive properties of microparticles/discs of betamethasone for the management of oral lichen planus.

This study involved the preparation and evaluation of buccal-mucoadhesive microparticles/discs of bethamethasone disodium phosphate (BDSP). The microparticles were prepared using the emulsion solvent diffusion method. Microparticles were prepared and characterized by encapsulation efficiency particle size, Fourier Transform Infra Red (FTIR) spectrums, Differential Scanning Calorimetric (DSC) thermograms and mucoadhesive properties. FTIR studies reported that BDSP was changed to bethamethasone base molecule inside the intact microparticles. The best drug to polymers ratio in microparticles was F1 containing 50 mg drug, 50 mg HPMC (as non-ionic and hydrophilic polymer) and 50 mg carbomer 934p (an anionic mucoadhesive polymer). The production yield of F1 microparticles was calculated as 78.60% with loading efficiency of about 65.14% and the mean particle size was also measured as 281.84 µm. It was proposed that during the microparticle preparation procedure, water soluble salt of the drug may be converted to the base which could be more effective in the buccal mucosa due to its higher partition coefficient and lipophilicity. The highest and lowest releases resulted from the discs prepared from F1 and F4, respectively, compared with the commercial tablet and untreated drug powder (p < 0.05). The data revealed that the discs exhibited good percentage of mucoadhesion (F1, 326 g/cm2). It may be concluded that drug loaded buccal-mucoadhesive microparticles are a suitable delivery system for BDSP, and may be used in the effective management of lichen planus.

Investigation of Possible Maillard Reaction Between Acyclovir and Dextrose upon Dilution Prior to Parenteral Administration.

In this study the stability of parenteral acyclovir (ACV) when diluted in dextrose (DEX) as large volume intravenous fluid preparation (LVIF) was evaluated and the possible Maillard reaction adducts were monitored in the recommended infusion time. Different physicochemical methods were used to evaluate the Maillard reaction of dextrose with ACV to track the reaction in real infusion condition. Other large volume intravenous fluids were checked regarding the diluted drug stability profile. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and mass data proved the reaction of glucose with dextrose. A Maillard-specific high performance liquid chromatography (HPLC) method was used to track the reaction in real infusion condition in vitro. The nucleophilic reaction occurred in diluted parenteral preparations of acyclovir in 5% dextrose solutions. The best diluent solution was also selected as sodium chloride and introduced based on drug stability and also its adsorption onto different infusion sets (PVC or non PVC) to provide an acceptable administration protocol in clinical practices. Although, the Maillard reaction was proved and successfully tracked in diluted solutions, and the level of drug loss when diluted in dextrose was reported to be between 0.27 up to 1.03% of the initial content. There was no drug adsorption to common infusion sets. The best diluent for parenteral acyclovir is sodium chloride large volume intravenous fluid.

The effect of emulgel preparation on the stability of Kojic acid in the topical anti-hyperpigmentation products.

BACKGROUND: The emulgel, a novel drug delivery system, merges emulsion and gel, offering advantages like enhanced stability, precise control over drug release kinetics, and increased drug absorption compared to emulsions alone. Kojic acid (KA) demonstrates potent inhibition of the tyrosinase enzyme, a crucial player in the melanin synthesis pathway. AIMS: The main objective of this experimental study is to formulate KA within an emulgel framework and assess its stability under various environmental conditions. METHODS: One percent of KA emulgel and 1% simple gel, serving as the control product, were supplemented with varying concentrations of sodium metabisulfite (SMBS) for its antioxidant properties. The formulations were segregated into four groups and subjected to diverse maintenance and stress conditions over a three-month period. Monthly evaluations of physicochemical alterations were conducted, initially employing digital photography, followed by the extraction of KA and subsequent quantification of its concentration through high performance liquid chromatography (HPLC). RESULTS: The best formulations for retaining KA among the prepared ones were the 0.25% SMBS KA emulgel and the 0.1% SMBS KA simple gel, capable of retaining 86% and 76% of the initial KA content under stress conditions, respectively (p < 0.0001). CONCLUSIONS: Regarding to this study, ideal storage condition for KA emulgel and simple gel is in the refrigerator temperatures. Moreover, optimal SMBS concentrations for stability enhancement are 0.25% for emulgel and 0.1% for the simple gel. A significant statistical difference was observed between refrigerated emulgel and simple gel in the retention of KA in the presence of optimum concentration of antioxidants (p < 0.0001).

Quantification of Arbutin and its degradation products, hydroquinone and p-Benzoquinone, in hyperpigmentation topical formulation: Effect of extraction procedure and interference assessment.

The utilization of Hydroquinone (HQ) in over-the-counter skincare items is subject to restrictions. Consequently, Arbutin (AR) serves as a reliable alternative for addressing hyperpigmentation in non-prescription topical formulations. Nevertheless, AR undergoes decomposition into HQ and p-Benzoquinone (BZ) when exposed to temperature stress, ultraviolet light, or dilution in an acidic environment, all of which can induce skin toxicity. The intention of this paper is to investigate the effect of extraction procedure on the conversion of AR to HQ and or BZ and to evaluate kinetics of AR hydrolysis to HQ. Meanwhile this study aims to evaluate AR and BZ interference with the United States Pharmacopoeia (USP) identification and assessment method for HQ Hydrolytic stress during extraction conditions underwent optimization through systematic screening tests. Subsequent assessment of the residual drug and its degradation products were achieved by HPLC method. The resulting data were meticulously fitted to various kinetic models. To analyze the potential interference of AR in HQ measurement using USP method, the standard concentrations of AR and HQ were analyzed through UV-VIS spectrophotometry. For enhanced certainty, a validated HPLC method analysis was also conducted. Notably, the acid hydrolysis of AR exhibited independence from its initial concentration. So, the hydrolytic degradation of AR exhibited a Zero-order kinetic profile. Furthermore, the proven interference of AR in the UV-VIS spectrophotometry method was identified within the context of the USP method. This study successfully utilized an adopted HPLC method for the concurrent quantification of AR, HQ, and BZ. The potential interference of AR in the UV-VIS spectrophotometric assay for HQ may lead to false results especially for regulatory purposes.

Efficient and straightforward spectrophotometric analysis of 5-hydroxymethylfurfural (HMF) using citrate@Fe3O4 nanoparticles as an adsorbent.

In this study, we developed a spectrophotometry method for the analysis of 5-hydroxymethylfurfuraldehyde (HMF) in pharmaceutical formulations using citrate@Fe3O4 adsorbent. As bare magnetite (Fe3O4) has certain limitations, such as aggregation and oxidation, surface modifications are commonly used to improve its properties. We successfully coated Fe3O4 with sodium citrate to create a magnetic adsorbent for isolating HMF from samples. We confirmed the successful surface coating of Fe3O4 with citrate using Fourier Transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Zeta potential, and scanning electron microscopy (SEM). The high adsorption capacity of citrate@Fe3O4 is due to the abundance of carboxyl and hydroxyl groups on the surface of the adsorbent, making it ideal for HMF extraction. The HMF concentration was then quantified using spectrophotometry. Citrate@Fe3O4 exhibited a high surface area and strong interaction with HMF. We analyzed the individual influential factors affecting the magnetic solid phase extraction (MSPE) setup. Validation parameters were also provided to confirm the reliability of the method. Under optimal parameters, the method exhibited excellent linearity in the range of 0.05-30.00 µg/ml with the lower limit of quantification (LLOQ) of 0.05 µg/ml. Relative standard deviations (RSD) values for precision were better than 10% and the method's trueness were better than 10%. Recoveries were found to be in the range of 85% to 106%, indicating excellent accuracy and reliability. We used this method to identify and measure HMF in six different dextrose pharmaceutical dosage forms as intravenous injectable solutions and three honey samples.

Design and optimization of sustained-release divalproex sodium tablets with response surface methodology.

Response surface methodology is defined as a collection of mathematical and statistical methods that are used to develop, improve, or optimize a product or process. In the present study, a statistical design (Mixture Design) was employed for formulation and optimization of a sustained-release hydrophilic divalproex sodium matrix tablet. Different excipients were used to improve the drug's poor flowability. The hardness of the prepared tablets and also their release pattern were tested. The formulation design was carried out employing mixture design using four excipients in three levels. The Carr's index of formulations and tensile strength were determined and analyzed using Minitab software. The suitable formulations regarding flowability and tablet tensile strength were selected by this software for subsequent drug release studies. The dissolution tests were carried out in acidic and basic phases which were previously proved to be biomimetic. Samples were analyzed using HPLC, and release data were compared to Depakine® (sustained-release divalproex from Sanofi). Release kinetics was also determined for selected formulations. Selected formulations were subjected to dissolution test and showed similar dissolution profiles with Depakine® based on difference and similarity factor calculations. The software selected an optimized formulation which had a slightly different release pattern in vitro compared to innovator but of nearly zero-order kinetics. It can be concluded that application of Mixture Design is a shortcut method to design suitable formulations of sustained-release divalproex sodium containing hydrophilic matrix tablets by direct compression method.

Deep eutectic solvent-based iron nanoparticles coated by N, S-doped amorphous carbon and its application in magnetic Dµ-SPE combined with DLLME for the extraction of PAHs in eyeliner.

This work presents a preparation of new magnetic nanoparticles coated with amorphous carbon and their application in dispersive solid-phase extraction in simultaneous extraction of sixteen polycyclic aromatic hydrocarbons from eyeliner. The extraction procedure was hyphenated with a lower density than water dispersive liquid-liquid microextraction (DLLME) for further preconcentration of the analytes to sensitive determination of them with gas chromatography-flame ionization detection. The magnetic adsorbent was prepared sonically from iron pentacarbonyl and then the nanoparticles were coated by N, S-doped amorphous carbon and the deep eutectic solvent prepared from tetrabutyl ammonium chloride and decanoic acid. The magnetic properties of the nanoparticles were studied by vibrating sample magnetometer. Also, scanning electron microscopy was used to investigate the nanoparticles morphology. The extraction procedure was done by migration of the analytes from eyeliner into a proper aqueous solution and their adsorption onto the nanoparticles. Then, the analytes were eluted and more concentrated by the DLLME approach. After validating the method, acceptable limit of detection and broad linear range were accessed in the ranges of 0.25-0.54 and 1.8-250 ng/g, respectively. Relative standard deviation values were ≤ 7.1% for the repeated analyses in the same day (n = 6) and different days (n = 6). Extraction recovery of the method was in the range of 79-96%. The introduced method was successfully used for the analysis of the PAHs in five eyeliner samples and only two of them were identified in all samples at ng/g level.

Argan oil as a pretreatment of human hair before exposure to oxidative damage: Attenuated total reflectance and protein loss studies.

INTRODUCTION: In recent years, argan oil has gained increasing interest in hair care products. In this study, attenuated total reflectance technique was utilized as a fast method and the results were compared to protein loss measurements in order to show the preventive effect of argan oil pre-treatment on excised human hair after oxidative hair damage. METHODS: Hair tresses were divided into three groups: in group-1; they were damaged using oxidant agent solely, in group-2 and 3; hair were pre-treated with argan oil before undergoing the oxidative damage. In group-2, the oil was removed by physical cleaning but in group-3 the oil was removed with a washing procedure. ATR (attenuated total reflectance) spectrum was recorded for different samples. Quantitative studies of protein loss in hair samples were performed by Lowry method. The antioxidant properties of argan oil were also measured in vitro using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) protocol, which determined the ability of the oil to scavenge the DPPH free radicals. RESULTS: The amount of protein loss with oil pre-treated groups was reduced significantly. The ATR spectrum showed oil deposition on hair even after washing. Four distinctive ATR peaks were changed during oxidation. The changes in peak height values were linear. The antioxidant property measured with DPPH method led to a IC50 value of 59 µg/ml. CONCLUSION: Argan oil pre-treatment was effective in protecting hair against oxidative damage. ATR outcomes were in accordance with protein loss results. In this study, the ATR testing method as a fast technique was used efficiently in quantification of hair damage.

Comparative Stability of Two Anti-hyperpigmentation Agents: Kojic Acid as a Natural Metabolite and Its Di-Palmitate Ester, Under Oxidative Stress; Application to Pharmaceutical Formulation Design.

Purpose: Kojic acid (KA) a natural metabolite and its dipalmitate ester, kojic acid dipalmitate(Kadp) are both prescribed to treat skin hyperpigmentation. Stress test reveals the intrinsicstability of active ingredients and leads to selection of the suitable formulations. This researchevaluates the comparative stability of KA and its di-palmitate ester under liquid oxidative stress. Methods: The HPLC-UV/PDA method with a C18 column was utilized. Liquid oxidative stresswas induced using hydrogen peroxide (H2O2). Degradation was separately induced for eachdrug, and they were compared to each other. Results: Kadp degraded more rapidly in similar liquid oxidative stress conditions than KA did.The superior degradation model was the first order for both drugs based on the mean percentage error (MPE) values, indicating the dependency of the reaction rate on the initial concentrationof the reactive substance. Ring opening was proposed as the most possible theory for KA andKadp oxidative degradation. Conclusion: It is suggested to use KA instead of Kadp in less stable formulations, such asextemporaneous preparations. The incorporation of antioxidant excipients in Kadp formulationsis recommended for yielding better stability results. Formulating Kadp in the internal phase ofo/w emulsion formulations may protect this susceptive molecule from oxidative degradationduring the shelf life of the pharmaceutical preparation. Further studies are required to study theexact mechanism of the degradation process.

Comparative physicochemical stability and clinical anti-wrinkle efficacy of transdermal emulgel preparations of 5% sodium ascorbyl phosphate and or ascorbic acid on human volunteers.

OBJECTIVES: Antioxidant containing cosmeceuticals are commonly prescribed products in treating wrinkles and revitalizing the skin. The aim of this study was the comparative evaluation of physicochemical stability and clinical anti-wrinkle efficacy of transdermal emulgel preparations of sodium ascorbyl phosphate (SAP) and ascorbic acid (AA) on human volunteers. METHODS: Emulgel preparations containing 5% of (SAP) and or (AA) were prepared. HPLC analysis was performed for stability evaluations. Clinical anti-wrinkle efficacy of the formulations was examined on human healthy volunteers in crow's feet area. Elasticity and digital images were recorded before and after treatment. RESULTS: Formulations with added antioxidants and kept in the refrigerator exhibited better stability characteristics. Two-sided blind study and placebo-controlled study showed that both actives were effective in wrinkles depth reduction and also elasticity enhancement but statistically significant difference in the efficacy of the products was not observed. CONCLUSION: Formulations containing (AA) and or (SAP) both improved elasticity and wrinkles of the skin almost by the same extent, and it is necessary to add antioxidant stabilizing agents to both preparations to reach a desired stability.

Differential Scanning Calorimetry and Fatty Acid Composition Analysis of Chocolates Marketed in Iran as an Alternative Method for Identification of Cocoa Butter Adulteration.

BACKGROUND: Cocoa butter (CB), an expensive product containing a specific triacylglycerol (TAG)composition, is often the object of economic adulteration. OBJECTIVE: The present study investigates the detection and quantification of cocoa butter substitutes (CBS) using differential scanning calorimetry. METHOD: CBS was mixed with CB (from 0 to 100%) as standard samples and analyzed using differential scanning calorimetry and gas chromatography to evaluate the thermal characteristics and fatty acid composition respectively. RESULTS: Increasing the ratio of CBS/CB changed the thermal parameters and fatty acid profiles significantly. For quantification of CBS in commercial samples, medium melting fraction temperature (TMMFvia r2 = 0.922) and melting enthalpy (ΔHfvia r2 = 0.972) were successfully used to quantify the value of CBS in the samples suspected of being fraudulent. According to the results, all of the thermal parameters increased significantly (P < 0.05) with increasing ratio of CBS/CB. It can be attributed to the presence of saturated fatty acids (C12-C22) in CBS which increases TLMF. CONCLUSIONS: The promising results of the present study could be used as a tool for the fast identification of adulteration and quantification of CBS in chocolate compositions. HIGHLIGHTS: Differential scanning calorimetry methods has been developed for identification of CB adulteration. CBS adulteration was detected in CB and also in commercial chocolate samples.

Thermal treating of acrylic matrices as a tool for controlling drug release.

The purpose of the present study was to investigate the effect of thermal-treating on the release of ibuprofen from the granules prepared using aqueous dispersions of Eudragit. To accomplish this goal, different formulations were prepared using wet granulation method containing two different types of Eudragit aqueous dispersions, RS30D, RL30D and Avicel as filler. Tablets were prepared using direct compression method. The prepared tablets were thermally treated at 50 and 70 degrees C for 24 h. The drug release from tablets was assessed before and after thermal-treating. The results of release study showed that, thermally-treating the tablets at the temperatures higher than glass transition temperature (Tg) of the polymer can decrease the drug release from matrices. For mechanistic evaluation of the effect of thermal-treating, powder X-ray diffraction (XPD), scanning electron microscopy (SEM), differential scanning calorimeter (DSC), Fourier transform infrared (FT-IR) and helium pycnometer have been employed. The SEM graphs showed that the tablets have smoother surface with less porosity after thermal-treating. FT-IR spectra showed no change in the spectrum of thermally-treated tablet compared to control. In DSC graphs, no crystalline change was seen in the heat-treated samples of ibuprofen tablets, but decreased and widened peak size were related to the probable formation of solid solution of ibuprofen in Eudragit matrix. The results of helium pycnometer showed a significant decrease in the total porosity of some heat-treated samples. This study revealed the importance of thermal treating on the drug release from sustained release tablets containing Eudragit polymer.

Assessment of feasibility of maillard reaction between baclofen and lactose by liquid chromatography and tandem mass spectrometry, application to pre formulation studies.

The aim of this study was to determine any possible, baclofen-lactose Maillard reaction products. Granules and tablets of baclofen and lactose were prepared and maintained in heat ovens for a certain time period. The effects of lactose type, addition of magnesium stearate, and water were monitored. Heated lactose and baclofen were analyzed using reverse-phase HPLC. Liquid chromatography tandem mass spectroscopy revealed nominal mass values consistent with baclofen-lactose, early-stage Maillard reaction condensation products (ESMRP). Multiple reaction monitoring confirmed the presence of ESMRP as well. FTIR analysis proved the formation of imine bond. The results indicated that baclofen undergoes a Maillard-type reaction with lactose.

Evaluation the Effect of Amine Type on the Non-isothermally Derived Activation Energy for the Interaction of 3 Antidepressant Drugs with Lactose.

Purpose: Evaluation of drug-excipients compatibility is an important stage during preformulation studies. In the present research, differential scanning calorimetry (DSC) at different heating rates (2.5, 10, 15°C/min) was applied for the kinetic evaluation of fluvoxamine (FLM), sertraline (SER) and doxepin (DOX) binary mixtures with lactose. Methods: Solid state kinetic parameters of the mixtures were calculated using two different thermal methods including ASTM E698 and Starink and the effect of amine type (pKa value) was investigated based on the calculated activation energies. Results: Based on obtained results mean activation energy calculated for FLM, SER and DOX with lactose using ASTM E698 and Starink methods are equal to 335.23, 132.02 and 270.99 kJ/ mol respectively. Conclusion: Results showed that the probability of drug-lactose interaction is higher in the SERlactose mixture in comparison with other two antidepressant drugs which is consistent with their pKa values.

Examining polyquaternium polymers deposition on human excised hair fibers.

BACKGROUND: Polyquaterniums (PQs) as important ingredients of hair products are synthetic cationic polymers and are used in commercial hair volumizers and conditioners. METHODS: Three different grades of polymers including PQ 87, 68, and 46 with various concentrations were used, and their hair deposition efficacy was measured at 5 different pH values using hair diameters measurements by digital micrometer. Deposition durability of polymer layer on the hair surface was tested by a defined washing test. Optical microscopic images and polarized light images were also taken from treated and untreated samples for further investigation. Attenuated total reflectance (ATR) spectral were recorded from hair samples to prove the polymer deposition and probable interaction with hair fibers. RESULTS: PQ-68 with the highest molecular weight (300 kDa) at pH = 9 exhibited the best hair deposition efficacy. The results revealed that the deposition of polymers is directly proportional to the pH values. The best results were seen at pH = 9, and at the lowest pH (pH = 5), the efficiency of polymers was approximately equal to zero. The best resistance against washing was shown by PQ-44 at pH = 6. ATR successfully tracked the presence of the polymers on the hair fibers and also proposed specific wave numbers for each polymeric agent, individually. CONCLUSIONS: In general, two main parameter which can mainly influence the deposition efficacy of PQs are the type of polymer or its molecular weight and also the positive charge density on the polymer molecules.

Analytical Investigation of the Possible Chemical Interaction of Methyldopa with Some Reducing Carbohydrates Used as Pharmaceutical Excipients.

Purpose: Assessment of drug substance and excipients compatibility is an important issue during pre-formulation studies as well as the quality control of pharmaceutical dosage forms. In this study, potential incompatibility between methyldopa and reducing excipients was evaluated using physicochemical methods. Methods: Dextrose and lactose (anhydrous & monohydrate) were selected as reducing carbohydrates. The initial incompatibility was studied with DSC and FTIR on binary mixtures with 1:1 mass ratio. Results were confirmed using HPLC studies coupled with mass spectrometry. Results: The DSC curves indicated the elimination of the melting endotherm of methyldopa in the binary mixtures. A new peak at 1719 cm-1 was observed in the FTIR spectra that can be attributed to the loss of type one amine functionality. The m/z of the proposed compound was observed in the mass spectra. Conclusion: The potential incompatibility of Methyldopa with reducing carbohydrates was established using physicochemical methods.

Thermal Stability and Kinetic Study of Fluvoxamine Stability in Binary Samples with Lactose.

Purpose: In the present study the incompatibility of FLM (fluvoxamine) with lactose in solid state mixtures was investigated. The compatibility was evaluated using different physicochemical methods such as differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy and mass spectrometry. Methods: Non-Isothermally stressed physical mixtures were used to calculate the solid-state kinetic parameters. Different thermal models such as Friedman, Flynn-Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) were used for the characterization of the drug-excipient interaction. Results: Overall, the incompatibility of FLM with lactose as a reducing carbohydrate was successfully evaluated and the activation energy of this interaction was calculated. Conclusion: In this research the lactose and FLM Maillard interaction was proved using physicochemical techniques including DSC and FTIR. It was shown that DSC- based kinetic analysis provides fast and versatile kinetic comparison of Arrhenius activation energies for different pharmaceutical samples.

Physicochemical analysis and nonisothermal kinetic study of sertraline-lactose binary mixtures.

In the present study the physicochemical stability of sertraline with lactose was evaluated in drug-excipient binary mixtures. Different physicochemical methods such as differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy, and mass spectrometry were applied to confirm the incompatibility. The final aim of this study was to evaluate the kinetic parameters using a fast and sensitive DSC method. Solid-state kinetic parameters were derived from nonisothermally stressed physical mixtures using different thermal models such as Friedman, Flynn-Wall-Ozawa, and Kissinger-Akahira-Sunose. Overall, the instability of sertraline with lactose was successfully evaluated. Further confirmation was made by tracking the Maillard reaction product of sertraline and lactose by mass spectrometry. DSC scans provided important information about the stability of sertraline in solid-state condition and also revealed the related thermokinetic parameters in order to understand the nature of the chemical instability.

Design and evaluation of 1- and 3-layer matrices of verapamil hydrochloride for sustaining its release.

The present study was performed to design oral controlled delivery systems for the water-soluble drug, verapamil hydrochloride, using natural and semisynthetic polymers as carriers in the forms of 1- and 3-layer matrix tablets. Verapamil hydrochloride 1-layer matrix tablets containing hydroxypropylmethylcellulose, tragacanth, and acacia either alone or mixed were prepared by direct compression technique. 3-layer matrix tablets were prepared by compressing the polymers as release retardant layers on both sides of the core containing the drug. The prepared tablets were subjected to in vitro drug release studies. Tragacanth when used as the carrier in the formulation of 1- and 3-layer matrices produced satisfactory release prolongation either alone or in combination with the other 2 polymers. On the other hand, acacia did not show enough prolonging efficiency in 1- and 3-layer matrix tablets. The results also showed that the location of the polymers in the 3-layer tablets has a pronounced effect on the drug release. Kinetic analysis of drug release from matrices exhibiting sustained release indicated that release was predominantly attributable to the contribution made by Fickian diffusion, while the erosion/relaxation mechanisms had a minor role in the release.