Giriraj T. Kulkarni

Development of novel gastroretentive drug delivery system of gliclazide: hollow beads

Abstract Aim: The current communication deals with the development of hollow floating beads of gliclazide. The primary effect of this drug is to potentiate glucose-stimulated insulin release from pancreatic islet-β-cells by induction of a decrease in potassium efflux from these cells. Because of the poor aqueous solubility, its absorption is limited. Thus, an attempt was made to improve its release profile. Methods: The hollow drug-loaded alginate beads in combination with low methoxyl pectin and hydroxypropylmethylcellulose (HPMC) were prepared by a simple ionotropic gelation method. The beads were evaluated for particle size and morphology using optical microscopy and scanning electron microscopy (SEM), respectively. Mucoadhesion test was done using goat stomach mucosal membrane. Release characteristics of the gliclazide-loaded hollow beads were studied in 0.1 N HCl (pH 1.2) and phosphate buffer (pH 5.8). Results: The developed beads were spherical in shape with hollow internal structure and had a particle size in the range of 0.730 ± 0.05 to 0.890 ± 0.03 mm. The incorporation efficiency of alginate -pectin beads was higher than alginate -HPMC beads. The Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction analysis showed stable character of drug in the drug-loaded hollow beads and revealed the absence of any drug -polymer interactions. The beads remained buoyant for more than 12 h. The drug release from beads followed Fickian diffusion with swelling. Conclusion: The preliminary results of this study suggest that the developed beads containing gliclazide could enhance drug entrapment efficiency, reduce the initial burst release and modulate the drug release.

Development of novel gastroretentive floating particulate drug delivery system of gliclazide.

The objective of present project was to improve the dissolution profile of gliclazide by developing floating alginate beads using various biodegradable polymers like gelatin, pectin and hydroxypropylmethylcellulose (HPMC). The floating beads were prepared by a simple ionotropic gelatin method using calcium carbonate as gas generating agent. The developed beads were characterized by Fourier transform infrared spectroscopy analysis, differential scanning calorimetry, X-ray diffraction analysis and scanning electron microscopy (SEM). The prepared beads showed good in vitro floatation, which was dependent on the concentration of gas-forming agent. SEM photomicrographs confirmed that the developed beads were spherical in shape and had particle size in the range of 730 to 890 μm. The incorporation efficiency was found to be in the range of 59.96 to 85.1%. The cumulative percent drug release from the beads after 10 h dissolution study at pH 1.2 and pH 5.8 was in the range of 33 to 46% and 82 to 95% respectively. The concentration of the gas generating agent was found to influence the release rate. The mechanism of drug release was Fickian diffusion with swelling. The in vivo sub-acute hypoglycemic study in high fat diet induced diabetic C57BL/6J mice demonstrated significant (p < 0.05) hypoglycemic effect over a period of 12 h and 24 h, respectively, with HPMC and pectin beads. A significant (p & 0.05) reduction in fasting and non-fasting blood glucose levels, reduction in fasting plasma insulin level and a significant improvement in glucose tolerance were observed in animals treated with formulations. The developed beads were suitable carriers for improving the systemic absorption of gliclazide and maintaining reduced blood glucose levels.

Natural mucoadhesive microspheres of Abelmoschus esculentus polysaccharide as a new carrier for nasal drug delivery

This work describes the preparation and evaluation of mucoadhesive microspheres, using Abelmoschus esculentus polysaccharide as a novel carrier for safe and effective delivery of rizatriptan benzoate into nasal cavity. The polysaccharide was extracted from the fruit of A. esculentus and mucoadhesive microspheres were prepared by emulsification, followed by crosslinking using epichlorohydrin. Prepared microspheres were evaluated for size, morphology, swelling properties, mucoadhesive strength, encapsulation efficiency and drug release. Microspheres were found to release 50% of drug within 15 min and rest of the drug was released within 60 min. The drug release was found to decrease with increasing concentration of polysaccharide. To determine the retention time of the microspheres in the nasal cavity of rabbits, the microspheres were radiolabelled with 99mTc and subjected to gamma scintigraphy. The results showed a significant improvement in the nasal retention of the microspheres as compared to the aqueous solution of radiolabelled free-drug.

Dual crosslinked pectin–alginate network as sustained release hydrophilic matrix for repaglinide

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1h. Developing a controlled and prolonged release delivery system is required to maintain its therapeutic plasma concentration and to eliminate its adverse effects particularly hypoglycemia. The present study aimed to develop controlled release repaglinide loaded beads using sodium alginate and pectin with dual cross-linking for effective control of drug release. The prepared beads were characterized for size, percentage drug entrapment efficiency, in vitro drug release and the morphological examination using scanning electron microscope. For the comparative study, the release profile of a marketed conventional tablet of repaglinide (Prandin® tablets 2mg, Novo Nordisk) was determined by the same procedure as followed for beads. The particle size of beads was in the range of 698±2.34-769±1.43μm. The drug entrapment efficiency varied between 55.24±4.61 to 82.29±3.42%. The FTIR results suggest that there was no interaction between repaglinide and excipients. The XRD and DSC results suggest partial molecular dispersion and amorphization of the drug throughout the system. These results suggest that repaglinide did not dissolve completely in the polymer composition and seems not to be involved in the cross-linking reaction. The percent drug release was decreased with higher polymer concentrations. In conclusion, the developed beads could enhance drug entrapment efficiency, prolong the drug release and enhance bioavailability for better control of diabetes.

Rheological characterization and controlled release properties of novel Abelmoschus moschatus mucilage based system

Present study was focused to investigate the anti-hyperlipidemic activity of Terminalia bellerica against high fat diet induced hyperlipidemia and obesity. Terminalia bellerica commonly known as Baheda is one of the most common plants being used in India since early times in many disorders one of the ingredients in many polyherbal formulations like Triphala etc used for cardiac disorders. The ethanolic extract of the fruits of Terminalia bellerica 250mg/kg & 500mg/kg body weight was administered p.o. for 20 days to test antihyperlipidemic activity. The parameters for evaluation of anti-hyperlipidemic activity are the physical parameters and the biochemical estimations. The physical parameters were gross examination of heart, heart weight: body weight ratio, liver weight, atherogenic index and basal metabolic index. In biochemical estimations various cardiac enzymes like lactate dehydrogenase, and the lipid profile were measured. The results of present study show that alcoholic extract of Terminalia bellerica (500 mg/Kg) has significant reduction in various lipid levels as well as the elevated physical parameters like heart weight: body weight ratio, body weight gain and BMI against high fat diet induced hyperlipidemia and obesity compared to clinically used drugs, Atorvastatin (10mg/kg) and Orlistat (pure drug 10mg/kg).Capecitabine, an effective anticancer drug in colorectal cancer chemotherapy, may create adverse side effects on healthy tissues. In the present study, we first induced colon adenocarcinoma with azoxymethane, a carcinogen agent, and then investigated the potentiality of polyamidoamine (PAMAM) dendrimer to improve capecitabine therapeutic index and decrease its adverse side effects on healthy tissues like liver and bone marrow. Other variables such as nanoparticle concentrations have also been investigated. Drug loading concentration (DLC) and encapsulation efficiency (EE) were calculated for capecitabine/dendrimer complex. Experimental results showed an increase in DLC percentage resulted from elevated capecitabine/dendrimer ratio. Capecitabine/dendrimer complex could reduce tumor size and adverse side effects in comparison with free capecitabine form.The strategy of price liberalisation and privatisation had been implemented in Sudan over the last decade and has had a positive result on government deficit. The investment law approved recently has good statements and rules on the above strategy to pharmacy regulations. Under the pressure of the new privatisation policy, the government introduced radical changes in the pharmacy regulations. To improve the effectiveness of the public pharmacy, resources should be switched towards areas of need, reducing inequalities and promoting better health conditions. Medicines are financed either through cost sharing or full private. The role of the private services is significant. A review of reform of financing medicines in Sudan is given in this study. Also, it highlights the current drug supply system in the public sector, which is currently responsibility of the central medical supplies public corporation (CMS). In Sudan, the researchers did not identify any rigorous evaluations or quantitative studies about the impact of drug regulations on the quality of medicines and how to protect public health against counterfeit or low-quality medicines, although it is practically possible. However, the regulations must be continually evaluated to ensure the public health is protected against by marketing high quality medicines rather than commercial interests, and the drug companies are held accountable for their conduct.

Development of Ocular Delivery System for Glaucoma Therapy Using Natural Hydrogel as Film Forming Agent and Release Modifier

BACKGROUND Glaucoma is characterized by increased intraocular pressure, which results in damage to the optic nerve. The existing therapy with conventional eye drops is inefficient due to nasolachrymal drainage, resulting in a reduced corneal residence of the drug. OBJECTIVES The objective was to develop controlled-release ocular films of timolol maleate using natural hydrogel from Tamarindus indica seeds as a sustaining and film-forming agent, to overcome the problems associated with eye drops. MATERIAL AND METHODS The hydrogel was isolated using hot aqueous extraction followed by precipitation with ethanol. Six batches of ocular films were prepared and evaluated for drug content, weight variation, thickness, diameter and in vitro release profile. The ideal batch of the films was subjected to stability, pharmacodynamic and ocular safety studies. RESULTS The yield of the hydrogel was 58.29%. The thickness of the ocular films was in the range of 0.17 to 0.25 mm and the weight of the films was found to increase with the increase in polymer content. The drug release from the films was found to be controlled over a period of 8 h. The films were found to be stable and were able to reduce the intraocular pressure for 24 h in a more efficient manner than the eye drops. The films were found to be practically non-irritating to the eye. CONCLUSIONS It can be concluded that the hydrogel from tamarind seeds can be used as a film-forming and release-controlling agent for the development of an ocular drug delivery system for the effective therapy of glaucoma.

Development and gamma-scintigraphy study of Hibiscus rosasinensis polysaccharide-based microspheres for nasal drug delivery

Abstract Objective: This work describes the application of natural plant polysaccharide as pharmaceutical mucoadhesive excipients in delivery systems to reduce the clearance rate through nasal cavity. Methods: Novel natural polysaccharide (Hibiscus rosasinensis)-based mucoadhesive microspheres were prepared by using emulsion crosslinking method for the delivery of rizatriptan benzoate (RB) through nasal route. Mucoadhesive microspheres were characterized for different parameters and nasal clearance of technetium-99m (99mTc)-radiolabeled microspheres was determined by using gamma-scintigraphy. Results: Their Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) studies showed that the drug was stable during preparation of microspheres. Aerodynamic diameter of microspheres was in the range 13.23 ± 1.83–33.57 ± 3.69 µm. Change in drug and polysaccharide ratio influenced the mucoadhesion, encapsulation efficiency and in-vitro release property. Scintigraphs taken at regular interval indicate that control solution was cleared rapidly from nasal cavity, whereas microspheres showed slower clearance (p < 0.005) with half-life of 160 min. Conclusion: Natural polysaccharide-based microspheres achieved extended residence by minimizing effect of mucociliary clearance with opportunity of sustained delivery for longer duration.