Search

Purpose: To assess the effect of polymer ratio on the quality of a novel co-processed excipient of prosopis gum and crab shell chitosan. Methods: The physicochemical properties (DSC thermogram, powder flow properties, porosity and swelling index as well as pH, viscosity and adhesive strength of 2 % w⁄v dispersions) of prosopis gum, chitosan and the three grades of co-processed excipient of prosopis gum and crab shell chitosan (Prosochit ® 201, Prosochit ® 101 and Prosochit ® 102) were determined. Results: The three grades of the co-processed excipient of prosopis gum and crab shell chitosan (Prosochit ® ) were characterized by one endothermic transition each with peaks at 180 o C, 179 o C and 178 o C for Prosochit ® 201, Prosochit ® 101 and Prosochit ® 102 respectively. Flow properties increased with increase in proportion of chitosan. The porosity of the three grades of the new excipient was not significantly different from that of prosopis gum. Swelling indices of prosopis gum, chitosan, Prosochit ® 201, Prosochit ® 101 and Prosochit ® 102 were 1135.53%, 14.00%, 726.33%, 677.33% and 514.00% respectively. The viscosity also decreased with increase in the proportion of chitosan. The new excipient had higher adhesive strength compared to the individual constituents (prosopis gum and crab shell chitosan). Conclusion: Prosochit ® is superior to its individual constituents as a tableting excipient but its suitability for liquid formulation is reduced by increase in the proportion of chitosan. Keywords: Polymer ratio, Crab shell chitosan, Prosopis gum, Prosochit ®

Purpose: To prepare and evaluate colon specific drug delivery system of diclofenac sodium for highly localized delivery to the colon.Methods: The colon specific drug delivery system was prepared as matrix-type microspheres using Ethyl Cellulose (EC), Cellulose Acetate Phthalate (CAP), and Eudragit L 100-55 by the Solvent Evaporation Method. Microspheres were evaluated for physical properties like drug content, particle size, bulk density and angle of repose.Results: The size range of the microcapsules was 228 to 608 μm while drug content was between 74.49 and 91.50 % depending on the polymer used and the polymer ratio. Mean bulk density was < 1.2 g/ml which indicates the good flow properties, while angle of repose was < 40 o, indicating free-flowing properties. The microspheres were spherical in shape with smooth and nonporous surface, except that the microspheres containing EC and CAP exhibited a rough and porous surface. The microspheres containing Eudragit L 100-55 in combination with other polymers gave better sustained release (78.9 and 76.6 % at the end of 8 h for formulation F4 and F5, respectively) than the others.Conclusion: Microspheres prepared with drug: EC: CAP ratio of 1:2:1 show the highest drug content, possess good flow properties and surface morphology, as well as promising drug release for colon specific drug delivery of diclofenac sodium for possible treatment of colorectal cancer.Keywords: Diclofenac, Colorectal cancer, Microspheres, Ethyl cellulose, Cellulose acetate phthalate, Eudragit L 100-55

Purpose: To investigate the effect of drug and polymer ratio on the physical characteristics and release rate of metformin hydrochloride from alginate microspheres.Methods: Microspheres were prepared by ionotropic gelation aerosolization technique using sodium alginate as polymer and calcium chloride as crosslinker. Three formulations of drug and alginate polymer ratios: 1:1 (F1); 1:1.5 (F2); and 1:2 (F3), and 10 % calcium chloride (CaCl2) were investigated. The microspheres were studied with respect to physical characteristics, release profile and release rate. Release evaluation was done at pH 1.2 in hydrochloric acid (HCl) for 2 h, and in phosphate-buffered saline (PBS) at pH 7.4 for 12 h.Results: Drug loading in formulations F1, F2 and F3 were 3.08 ± 0.21, 3.34 ± 0.28, and 3.99 ± 0.19 %, respectively. Low entrapment of below 15 % was achieved for all formulations, whereas high yield (above 45 %) was obtained. Drug release above 74 % was observed for all formulations. The release rates of F1, F2 and F3 were 9.6390 x 10-2, 9.0985 x 10-2, and 8.3312 x 10-2 %/min, respectively.Conclusion: Metformin-alginate microspheres can be used for optimized formulations with good physical characteristics and in vitro release. These findings suggest that the microspheres might be a potent drug delivery system for the treatment of diabetic mellitus.Keywords: Metformin, Alginate microspheres, Drug-polymer ratio, Aerosolization, Drug release

Purpose: To enhance the dissolution of albendazole (ABZ) using spray-drying technique.Method: ABZ binary mixtures with Kollicoat IR® (KL) and polyvinyl pyrrolidone (PVP) in various drug to polymer ratios (1: 1, 1: 2 and 1; 4) were prepared by spray-drying. The spray-dried particles were characterized for particle shape, and dissolution rate as well as by differential scanning calorimetry(DSC) and Fourier transform infrared (FTIR).Results: Scanning electron micrographs showed a homogeneous distribution of ABZ in the polymer matrix for ABZ-PVP spray-dried system in ratios of 1: 2 and 1: 4, while it was observed only upon using a ratio of ABZ: KL 1: 4 in case of ABZ-KL systems. FT-IR spectra of both physical mixtures and spraydried mixtures did not show any change for all ABZ-polymer systems, thus indicating the compatibility of the carriers with ABZ. ABZ exhibited a noticeable enhanced dissolution rate from its spray-dried coacervate with PVP and this was independent of the drug/polymer ratio. Drug release was 78, 81 and 81 % from the spray-dried ABZ-PVP systems of drug: polymer ratio of 1:1, 1:2 and 1: 4, respectively, within 5 min. Drug showed complete dissolution within 15 min. On the other hand, enhancement of dissolution rate varied with ABZ: Kl ratio.Conclusion: Enhancement of ABZ dissolution for both types of spray-dried particles is due to the reduction in drug particle sizes, wetting of the dissolution medium by the hydrophilic carriers and the amorphosization of the drug crystals by the carriers.Keywords: Albendazole, Spray-drying, Kollicoat, Polyvinyl pyrrolidone, Dissolution, Amorphous

Purpose: To formulate simvastatin orodispersible tablets with high dissolution rate and enhanced bioavailability. Methods: Simvastatin solid dispersions in β- cyclodextrin, hydroxylpropyl-β-cyclodextrin, and hydroxylbutyl-β-cyclodextrin were prepared in different drug: polymer ratios by kneading and solvent evaporation methods. Compatibility was investigated by Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) Based on the results of solubility studies, the most suitable solid dispersion was selected and formulated into orodispersible tablets using Emcosoy and Kpolacrillin as superdisintegrants, and mannitol and Pullulan as diluents. The tablets were evaluated for wetting and disintegration times, water absorption, and in vtro dissolution. Results: Increase in drug solubility was dependent on polymer type, concentration and preparation method. Simvastatin-hydroxylbutyl-β-cyclodextrin solid dispersion mixture prepared in 1:2 drug: polymer ratio by solvent evaporation method had a higher solubility than other dispersions. DSC and FTIR indicated the formation of solid dispersion without chemical interaction between simvastatin and polymer. Orodispersible tablet prepared with Emcosoy and Pullulan showed least wetting and disintegration times (20 and 35 s, respectively), fastest water sorption rate, and the highest dissolution rate (100 % after 20 min). Conclusion: Orodispersible tablets prepared with Emcosoy as superdisintegratnt and Pullulan as diluents and containig simvastatin solid dispersion in hydroxylbutyl-β-cyclodextrin provides optimum water solubility and hence, drug bioavailability.

Purpose : To formulate and prepare controlled release (CR) matrix tablets of tramadol HCl using Carbopol 974P and 934 polymers as rate-controlling agents. Methods : The tablets were prepared by direct compression method using various drug to polymer (D:P) ratios. Co-excipients, including carboxymethylcellulose, starch and/or hydroxypropyl methylcellulose were also used to modulate the formulations. Various physical tests and in vitro dissolution studies were carried out on the formulations. The dissolution data were subjected to various release models Results : As the concentration of the polymer (rate-controlling agent) increased, dissolution rate decreased, For the formulation containing Carbopol 974P at D:P ratio of 10:7, drug release decreased to 83 % compared with the release rate of 99 % for the formulation with D:P ratio of 10:3. Kinetic analysis indicates that drug release mechanism was anomalous non-Fickian diffusion. Conclusion : Both Carbopol 974P and 934 can be used as rate-controlling agents in the formulation of tramadol HCl CR tablets. Appropriate selection of drug/polymer ratio can be applied effectively to modulate the dissolution rate of the drug. Keywords : Tramadol, Carbopol, Carboxymethylcellulose (CMC), Hydroxypropyl methylcellulose, Controlled release

Purpose: To formulate and characterize nanoparticles containing silybin, and evaluate their activity against carbon tetrachloride (CCl 4)-induced liver toxicity. Methods: Silybin nanoparticles were formulated by o/w emulsion solvent evaporation technique using poly-e-caprolactone as polymer. Four different nanoparticle formulations (NP 1, NP 2, NP 3 and NP 4) were prepared by varying the drug/polymer ratio. The particles were characterized for particle size, drug content and in vitro drug release. The pharmacokinetics and pharmacodynamics of the silybin formulations in male Wistar rats were evaluated following i.v. administration, using silybin solution as reference. The hepatoprotective activity of the formulations was also determined in a CCl 4-treated rat model. Results: Silybin nanoparticles were successfully prepared using o/w emulsion solvent evaporation technique. The nanoparticles sustained the release of the drug both in vitro and in vivo for up to 10 days and offered better pharmacokinetic properties than the free drug itself. Intravenous nanoparticulate administration reversed serum liver enzyme levels by 95 % compared to only 50 % for the drug solution. Conclusion: The developed silybin nanoparticles showed superior pharmacokinetic properties and hepatoprotective activity to silybin solution.

Purpose: To formulate and evaluate glibenclamide (GB)-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) for controlled release.Methods: GB-loaded PLGA NPs were prepared by solvent evaporation technique using methanol/dichloromethane (2:1) and characterized by transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). The effect of stirring speed (250, 1000, 1500 and 2500 rpm) and drug: polymer ratio (1:1, 1: 2, 1:3 and 2:1) on particle size, size distribution, zeta potential, drug loading, encapsulation efficiency and drug release was also studied.Results: Stable NPs were successfully prepared without any incompatibility, as indicated by TEM and DSC studies, respectively. As polymer and drug concentrations, and stirring speed increased, particle size, drug loading and encapsulation efficiency also increased. Increase in polymer concentration sustained drug release but reverse was obtained as drug concentration increased.Conclusion: Controlled release biodegradable glibenclamide NPs can be efficiently prepared by emulsification solvent evaporation method suitably modulating processing variables.

Purpose: To prepare and evaluate metformin microspheres for prolonged release. Methods: Metformin microspheres were prepared by non-aqueous solvent evaporation method using various polymers, including ethylcellulose (EC), hydroxypropyl methylcellulose (HPMC), carbopol 934P (CA) and chitosan (CH). The effect of process variables, viz, drug/polymer ratio, stirring rate and type of polymer on the mean particle size, drug entrapment efficiency, yield, drug content, micromeritic properties and drug release of the microspheres were studied. Results: It was observed that as the stirring speed increased from 600 to 1800 rpm, microsphere size decreased and hence drug release rate increased. Drug release rate at 1:2 drug: polymer for microspheres produced at a stirring rate of 1200 rpm was in the following order: carbopol 934P > HPMC > ethyl cellulose > chitosan. The formulations containing carbopol 934P (CA3) and HPMC (HPMC3) released drug faster than chitosan microspheres (CH3). Conclusion: Amongst the developed microspheres, CH3 formulation (with chitosan as the polymer) exhibited maximum prolonged drug release at gastrointestinal pH or at least 15 h. This oral sustained metformin formulation could potentially improve the bioavailability of the drug as well as patient compliance. Keywords: Metformin, Microspheres, Prolonged release, Solvent evaporation, Ethylcellulose, Hydroxypropyl methylcellulose, Chitosan

Purpose: To formulate biodegradable chitosan microspheres loaded with famotidine to overcome the poor bioavailability and frequent dose administration of the drug.Methods: Chitosan microspheres were prepared by simple emulsification technique based on glutaraldehyde crosslinking. Various process and formulation variables such as speed of emulsification, crosslinking time, drug/polymer ratio, volume of cross linking agent and volume of surfactant were optimized. The microspheres were characterized for entrapment efficiency, drug loading, in vitro drug release, surface morphology, as well as by particle size analysis, Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC).Results: The microspheres showed a smooth surface with a narrow particle size distribution (105 – 219 μm) and an entrapment efficiency of up to 73 %. They exhibited controlled drug release characteristics with 85.6 % of the drug released over a period of 24 h with an initial burst release of 26.9 % in the first 2 h. Drug release followed Higuchi release kinetics. FTIR and DSC data indicate that there was no drug interaction between the drug and polymer used.Conclusion: The chitosan microspheres could be further developed as a potential biodegradable carrier for oral controlled delivery of famotidine.Keywords: Chitosan microspheres, Crosslinking, Controlled delivery, Famotidine, Glutaraldehyde, Biodegradable.

Purpose: To evaluate physicochemical changes in ciprofloxacin following incorporation in Carbopol polymeric composites.Methods: The ciprofloxacin and Carbopol were mixed in water in a drug:polymer ratio of 1:5 (w/w) and homogenized to produce uniform composites. X-ray powder diffraction analysis of the pure ciprofloxacin and the Carbopol polymeric composites of the drug were obtained using a powder diffractometer. Spectra for the materials were also generated by Fourier transform infrared (FTIR) spectroscope interfaced with an infrared (IR) microscope operated in reflectance mode.Results: Based on the Hanawalt system, three prominent x-ray diffractogram (XRD) peaks of the pure ciprofloxacin and the drug in the polymeric composites exhibited d-spacing at similar 2θ values, but the relative intensity of these peaks was higher in the polymeric composites. FTIR analysis indicates that there were intermolecular hydrogen bonding and esterification between the drug and polymer in the polymeric composites.Conclusion: The changes that occurred in ciprofloxacin indicate increase in stability, decrease in solubility and delayed release of the drug from polymeric composites which could facilitate the formulation of a sustained release form of the drug.Keywords: Ciprofloxacin, X-ray diffraction, Fourier transform infrared, Carbopol, Polymeric composites

Purpose: To formulate theophylline microspheres with cellulose acetate using solvent evaporation method and evaluate the effect of various processing factors on their characteristics. Methods: Microspheres containing theophylline were prepared with a hydrophilic, biocompatible polymer - cellulose acetate - by an emulsion solvent evaporation technique using an acetone/liquid paraffin system containing Span 80 as a surfactant. The effect of processing factors, e.g., varying drug/polymer ratio (1:1, 1:2, 1:3) and temperature (10 and 35 °C) on microsphere characteristics and drug release were examined. Similarly, microspheres with a drug/polymer ratio of 1:3 incorporating Span 20 were also also prepared and evaluated. Results: The microspheres were white, free-flowing and spherical. The yield varied from 73.0 to 87.5 % while entrapment efficiency was in the region of 71.8 to 92.4 %. High drug/polymer ratio, Span 80 (surfactant) and processing temperature between 10 and 30 °C produced formulations with better drug entrapment efficiency. High drug/polymer ratio, low processing temperature and low HLB value of surfactant enhanced the sustained drug release characteristics of the microspheres. Conclusion: The combination of three suitable factors - Span mixture (with HLB value of 4.3), processing temperature of 10 °C and drug/polymer ratio of 1:3 - produced a suitable controlled release theophilline microsphere formulation which could be effective for the management of asthma.

Purpose: The purpose of this work was to develop a prolonged microsponge drug delivery system containing dicyclomine. Methods: Dicyclomine-loaded, Eudragit-based microsponges were prepared using a quasi-emulsion solvent diffusion method. The compatibility of the drug with formulation components was established by differential scanning calorimetry (DSC) and Fourier transform infra-red (FTIR). Process parameters were modulated to optimise the formulation. Shape and surface morphology of the microsponges were examined using scanning electron microscopy. Results: The results of compatibility tests showed that no chemical interaction or changes took place during preparation of the formulations; furthermore, the drug was stable in all the formulations. In increase in drug:polymer ratio resulted in a reduction in the release rate of the drug from the microsponges. Kinetic analysis showed that the main mechanism of drug release was by Higuchi matrixcontrolled diffusion. Drug release was bi-phasic with an initial burst effect with 16 – 30 % of the drug was released in the first hour. Cumulative release for the microsponges over 8 hours ranged from 59 - 86 %. Conclusion: This study presents an approach for the modification of microsponges for prolonged drug release of dicyclomine. The unique compressibility of microsponges can be applied to achieve effective local action since microsponges may be taken up by macrophages present in colon.Keywords: Microsponge; Dicyclomine; Quasi-emulsion solvent diffusion; Eudragit RS-100; Colonic drug release

Purpose: The aim of the work was to prepare nitrendipne-loaded Eudragit RL 100 microspheres to achieve sustained release nitrendipine. Method: Nitrendipne-loaded Eudragit RL 100 microspheres were prepared by an emulsion-solvent evaporation method using ethanol/liquid paraffin system. The resultant microspheres were evaluated for average particle size, drug loading, in vitro drug release and release kinetics. FTIR spectrometry, scanning electron microscopy, differential scanning calorimetry and x-ray powder diffractometry were used to investigate the physical state of the drug in the microspheres. Result: The mean particle size of the microspheres was influenced by varying drug:polymer ratio and emulsifier concentration while drug loading was dependent on drug:polymer ratio. The results of FTIR spectrometry, differential scanning calorimetry and x-ray diffractometry indicated the stable character of nitrendipne in drug-loaded microspheres and also revealed absence of drug-polymer interaction. The drug release profiles of the microspheres at pH 1.2 showed poor drug release characteristics while at pH 6.8, drug release was extended over a period of 8 h; release was influenced by polymer concentration and particle size. Drug release followed the Higuchi model. Conclusion: The nitrendipine-loaded Eudragit RL 100 microspheres prepared under optimized conditions showed a good sustained release characteristics and were stable under the conditions studied Keywords: Nitrendipine, Eudragit RL 100, Microspheres, Physicochemical characterization, Sustained release. Tropical Journal of Pharmaceutical Research Vol. 7 (3) 2008: pp. 1033-1041

Purpose: The aim of this work was to formulate sodium alginate nanospheres of amphotericin B by controlled gellification method and to evaluate the role of the nanospheres as a “passive carrier” in targeted antifungal therapy. Methods: Sodium alginate nanospheres of amphotericin B were prepared by controlled gellification method, and the particle size analysis was carried out by scanning electron microscopy. The carrier capacity of sodium alginate was evaluated in terms of drug to polymer ratio. In vitro release study was carried out on all drug loaded nanospheres by the dialysis method. Release kinetics of drug from different drug loaded nanospheres was also determined. The in vivo antifungal efficacy of nanospheres bound drug vis-à-vis the free drug was evaluated in candidiasis- induced mice models. Results: Preparation of nanospheres through controlled gellification method yielded particles with a size range of 419.6 ± 0.28 nm. Studies on drug to polymer ratio showed a linear relationship between concentration of drug and drug loading capacity. In vitro release kinetic study revealed that the release of drug from the nanospheres followed Fickian diffusion. In vivo studies showed that the nanosphere-bound drug produced a higher antifungal efficacy than the free drug. Conclusion: The formulated sodium alginate nanospheres containing amphotericin B was found to have better antifungal activity when compared to the free drug and also yielded sustained in vitro release. Keywords: Nanospheres, sodium alginate, amphotericin B, controlled gellification method, in vitro & in vivo release > Tropical Journal of Pharmaceutical Research Vol. 6 (1) 2007: pp. 653-659

Purpose: Lipid nanospheres are used for the passive targeting of cosmetic agents to skin, thereby achieving major benefits such as reduction of total dose and avoidance of systemic absorption. The present study was carried out to exploit the feasibility of using polymeric nanospheres as an alternative and cheaper carrier for targeting corticosteroids to the skin. Methods: Nanospheres were prepared from ethyl cellulose by a modified method of desolvation and cross linking. The drug betamethazone was incorporated into nanospheres and the drug: polymer ratio was evaluated to determine the carrier capacity of the polymer. In-vitro release studies of drug-loaded nanospheres were carried out by the centrifugal ultrafiltration method. The kinetics of release was determined and fitted to an empirical equation. The release of drug from drug-loaded nanospheres dispersing in a conventional cream was evaluated. A comparative in-vitro diffusion study was carried out between a commercial brand of cream and the cream incorporating nanospheres. Results: Formulation of nanospheres of betamethazone by a modified method produced discrete particles. Studies on drug:polymer ratio showed a linear relationship between drug concentration and percentage of loading. The in-vitro release of drug-loaded nanospheres was found to be first order. The comparative in-vitro diffusion study between the commercial cream and the formulated cream showed a marked reduction in release rate from nanospheres-bound cream. Conclusion: Formulated topical cream containing nanospheres of betamethazone was found to be a potential dermal delivery system for sustaining the release of the drug. Keywords : Nanospheres, desolvation and cross-linking method, ethyl cellulose, betamethazone, in-vitro diffusion studies. > Tropical Journal of Pharmaceutical Research Vol. 4 (2) 2005: pp. 495-500

Purpose: The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of a highly water-soluble drug, stavudine, using Copolymers synthesized from acrylic and methacrylic acid esters (Eudragit RS 100 and RL 100) as the retardant material. . Methods: Microspheres were prepared by solvent evaporation method using an acetone / liquid paraffin system. Magnesium stearate was used as the droplet stabilizer and n-hexane was added to harden the microspheres. The prepared microspheres were characterized for their micromeritic properties and drug loading, as well by fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry, x-ray powder diffractometry and scanning electron microscopy. The in vitro release studies were performed in pH 6.8, phosphate buffer. Results: The prepared microspheres were white, free flowing and spherical in shape. The drug-loaded microspheres showed 67-91% of entrapment and release was extended upto 6 to 8 h. The infrared spectra and differential scanning calorimetry thermographs showed stable character of stavudine in the drug-loaded microspheres and revealed the absence of drug-polymer interactions. X-ray diffraction patterns showed that there was decrease in crystallinity of the drug. Scanning electron microscopy study revealed that the microspheres were spherical and porous in nature. Conclusion: The best-fit release kinetics was achieved with Higuchi plot followed by zero order and First order. The release of stavudine was influenced by the drug to polymer ratio and particle size & was found to be diffusion controlled. Keywords: Stavudine, Eudragit, microspheres, controlled release, polymethacrylate > Tropical Journal of Pharmaceutical Research Vol. 4 (1) 2005: pp. 369-375