OPTIMIZATION OF FORMULATION OF SOLID DISPERSION OF FUROSEMIDE BY FACTORIAL DESIGN

Objective: The present study aimed to improve the rate of dissolution of furosemide by solid dispersion technique. Methods: Solid dispersion of furosemide was prepared by using hydrogel isolated from the seeds of Lepidium sativum as a novel carrier by the solvent evaporation method. Solid dispersion was evaluated to study the improvement in the rate of dissolution. Molecular dispersion of furosemide in the novel carrier was studied by DSC and FTIR studies. Solid dispersion was filled in capsules after stability studies and the formulation was optimized by adopting factorial design. Results: Solid dispersion of furosemide exhibited dissolution improvement from 13.54 % (plain furosemide) to 69.12% (solid dispersion) in the first 60 min. Improvement in dissolution efficiency was found to be retained after stability studies. Capsules were filled with the formulation of solid dispersion using two different grades of lactose-α lactose monohydrate and anhydrous lactose and were found stable after stabilization studies. Conclusion: The dissolution improvement of furosemide was attributed to its molecular dispersion in the novel carrier selected for this study. The recrystallization of furosemide was prevented due to intermolecular interaction between the novel carrier and furosemide. This was confirmed by FTIR. Evaluation of the dissolution data of factorial batches was analyzed by ANOVA. Analysis of the data revealed that selected levels of α lactose monohydrate and anhydrous lactose would be useful to navigate design space

STUDY OF THE FUNCTIONALITY OF A NOVEL SOLUTION BINDER OBTAINED FROM OCIMUM BASILICUM SEEDS: A MECHANISTIC APPROACH

Objective: The aim of the present study was to investigate the functionality of the hydrogel isolated from the seeds of Ocimum basilicum (Gel) as a novel solution binder. Methods: Paracetamol is known to possess poor manufacturability. Therefore it was selected as a model drug to study the efficiency of Gel as a solution binder. Paracetamol tablets were prepared at gradually increasing compression pressure from the granules prepared by using Gel of various viscosities as a solution binder. Compactibility parameter was calculated to assess the utility of Gel as a novel tablet binder. Optimization of the formulation was done by adopting factorial design as an appropriate DOE. Tablets of factorial batches were evaluated for disintegration time and crushing strength. The effect of viscosity of binder solution used to prepare granulation and compression pressure applied on granulation on the performance of the tablets was confirmed by analyzing the data using ANOVA. Results: The addition of binder solution to prepare granulation with the viscosity ≥ 19.33 centipoises was found to be suitable to attain desired degree of agglomeration. The crushing strength of the tablets was found to be increased with an increase in compression pressure and an increase in viscosity of binder solution. Conclusion: The compatibility parameter was observed to be increased as the viscosity of the binder solution added in the formulation was gradually increased. The Gel as a binder material was found to deform plastically at compression pressures 34.48 to 75.85 MPa. This confirmed its functionality as a solution binder in Paracetamol tablet preparation

FORMULATION AND EVALUATION OF RACECADOTRIL MUCOADHESIVE MICROSPHERES

Objective: To develop and evaluate the mucoadhesive microsphere using combinations of natural polymers chitosan and xanthan gum for sustained release. Methods: In the present work mucoadhesive microspheres were prepared by using natural polymers like chitosan and xanthan gum by using the emulsion chemical cross-linking method. Chemical cross-linking was done by using glutaraldehyde. The 22 factorial design was employed to show the effect of cross-linking agent and processing factor-like stirring and speed. Prepared microspheres were evaluated for their particle size, surface morphology, drug entrapment efficiency, in vitro drug release, swelling index, and mucoadhesive strength. Results: The size of microspheres of factorial batches were in the range of 26-46 µm. The swelling index was showed in the range of 1.51-1.66 percentage. The equation of multiple regression revealed that there was significant interaction among factors. The glutaraldehyde concentration had a positive effect on % entrapment efficiency, % cumulative drug release and % mucoadhesion. Stirring speed showed a negative impact on % entrapment efficiency, % cumulative drug release and % mucoadhesion. The interactive effect of glutaraldehyde concentration and the stirring speed was found to be positive for % entrapment efficiency and % cumulative drug release. In vitro drug release study of optimized formulation F2 show 96 % of drug release with 6 h indicating sustained release behavior with diffusion mechanism. The SEM image of the optimized batch was spherical with a porous surface. Conclusion: The results obtained in this research work indicated that a promising potential of chitosan and xanthan gum combination for the preparation of the mucoadhesive microsphere of Racecadotril

Formulation and evaluation of gastro retentive tablets of clarithromycin prepared by using novel polymer blend

Clarithromycin is a semi synthetic macrolide antibiotic that is proved to be extremely effective mono therapy in treating H. pylori infection. One of the various reasons reported for partial eradication of H. pylori infection is that the short dwelling time of antimicrobial agents in the stomach. Hence the principal object of the present work was to design and develop floating and swellable gastro retentive tablet of clarithromycin to obtain its prolonged release in the stomach. HPMC K 100LV was blended in the present study with the Gel isolated from the seeds of Ocimum basilicum to overcome the drawback of time dependent erosion of former. This novel polymer blend was investigated and exploited as a matrix material for the development of gastro retentive tablets of clarithromycin as drug delivery system. Hydrogen bonding between the Glucomannan – a component of the Gel and HPMC K100LV was envisaged and further confirmed by ATR-FTIR. Tablets of clarithromycin prepared by using the polymer blend of Gel and HPMC K100LV exhibited fast swelling with almost instantaneous buoyancy followed by prolonged release of drug from the swollen, floating dosage form. The retention of the optimized tablet formulation of clarithromycin in the stomach was confirmed by γ scintigraphy. Keywords: Polymer blend, Ocimum basilicum, Gamma scintigraphy, Gastroretentive tablet, Clarithromyci

Formulation Development and in-vivo/in-vitro Characterization of Novel Glucose Responsive Hydrogel for Insulin Delivery: Glucose Responsive Insulin Delivery

Glucose-responsive delivery systems intelligently regulate insulin release in response to fluctuating blood glucose levels, offering a more controlled approach to diabetes management. The current study introduces a novel glucose-responsive hydrogel system for enhanced insulin delivery. The hydrogel, formulated from chitosan and Poloxamer 407, exhibits unique thermo-responsive and pH-sensitive characteristics, making it suitable for subcutaneous insulin delivery. The research encompasses comprehensive in vitro and in vivo analyses to evaluate the formulation's efficacy and responsiveness to glucose concentrations. In vitro studies demonstrated that the hydrogel's solubilization rate varies with pH and glucose levels, crucial for controlled insulin release. Notably, the hydrogel exhibited an extended and more stable control of blood glucose levels compared to conventional insulin treatments. One significant finding is the hydrogel's rapid in vivo gelation and biodegradability, indicating its safety and effectiveness in a physiological environment. In vivo experiments conducted on diabetic rats showcased the hydrogel's glucose-responsive behavior. Moreover, the hydrogel's ability to modulate insulin release in response to changing glucose levels was distinct from traditional insulin therapies, highlighting its potential to manage multiple hyperglycemic episodes after a single dose. Overall, this research marks a significant advancement in insulin delivery systems. The development of this glucose-responsive hydrogel system presents a promising approach for achieving more controlled and stable blood glucose levels in individuals with diabetes, potentially enhancing their quality of life. The findings suggest opportunities for further optimization, particularly in insulin content, to tailor the system to the specific needs of the diabetic population

Formulation and Evaluation of Transdermal patches of Ropinirole HCl

ABSTRACT The conventional multidose antiparkinsons therapy leads to re-emergence of Parkinson's symptoms, due to fluctuations in serum levels of drug. The rational strategy to overcome this drawback is to minimize the fluctuations by fabricating sustained release formulations. Ropinirole HCl is a drug used to treat Parkinson's disorder and it is suitable drug candidate for transdermal delivery due to its small molecular size, optimum log P and low oral bioavailability due to first pass metabolism. Hence the present study was aimed at development of transdermal patch of Ropinirole HCl to show its prolonged release. The combination of HPMC K15 and Eudragit RL100 was tried as a porous matrix to control the release of Ropinirole HCl up to 12 hrs. The transdermal patches were prepared by solvent casting method. All the patches were evaluated for the permeation along with physical studies including appearance, thickness, folding endurance, drug content, percentage of moisture content and percentage of moisture uptake. The results of physical parameters ensured integrity, stability and applicability of the patches. The results of permeation studies clearly indicated that the release pattern of Ropinirole HCl can be controlled by maintaining appropriate proportion of HPMC K15 and Eudragit RL 100 in the matrix. No erythma was found within 12 hr after application of optimized transdermal patch when compared with standard irritant. Thus this formulation was suitable for transdermal application

PREPARATION AND EVALUATION OF CO-CRYSTALS OF CARBAMAZEPINE WITH GLUCOMANNAN

Objective: The objective of the present work was to inhibit transformation of carbamazepine anhydrous to its dihydrate form in aqueous medium by adopting the co-crystal approach.Methods: Co-crystallization of carbamazepine and glucomannan as co-former was carried out by solution mediated phase transformation. The solution of carbamazepine and glucomannan in ethanol (95%) was agitated for 2 h and the co-crystals obtained were recovered after 24 h.Results: Co-crystal formation due to hydrogen bonding between carbamazepine and glucomannan as a co-former was confirmed by FTIR study. Inhibition of transformation of co-crystal of carbamazepine to carbamazepine dihydrate in aqueous medium was confirmed by SEM.Conclusion: Inhibition of transformation of carbamazepine co-crystal to its dihydrate form resulted in its improved dissolution. Dissolution efficiency of carbamazepine in its co-crystal was increased up to 79.26% within 30 min

FORMULATION OF NANOSTRUCTURED LIPID CARRIERS OF HALOPERIDOL PREPARED BY USING CLARIFIED BUTTER

Objective: To develop the nanostructured lipid carriers (NLC’s) using clarified butter.  Methods: Haloperidol loaded micro emulsion templates were prepared by using Smix of Tween 80 and propylene glycol in the ratio 1:2. The selection of the mixture of surfactant and co-surfactant (Smix) and their appropriate proportion were decided by the traditional way of construction of pseudo ternary phase diagrams. 22 factorial design was used to check the amenability of the formulation for its successful scale-up. Sonication time and the amount of Smix were selected as independent variables and their influence on the globular size (Y1) of the micro emulsions formed was evaluated by using statistical models. Composition of optimized micro emulsion template was further used to prepare haloperidol loaded NLC’s by ‘micro emulsion quenching method’. Results: The micro emulsion formulations containing Tween 80 as a surfactant and propylene glycol as a co-surfactant exhibited the smallest globular size and hence this composition was used further to implement factorial design as design of experiments.  The statistical analysis of the data suggested that the micro emulsion formulation can be scaled up successfully. NLC’s were prepared from the optimized micro emulsion formulation as template. The globular size of NLC’s was confirmed by Transmission Electron Microscopy and was observed to be in the range of 300 to 600 nm. Conclusion: The present work suggested that the latency of the clarified butter as a natural blend of solid lipid and liquid lipids can be successfully explored to prepare nanostructured lipid carriers

Formulation and Evaluation of Solid Dispersions of Furosemide in Sodium Starch Glycolate

Purpose: This investigation was carried out to determine if a solid dispersion of furosemide in sodium starch glycolate (SSG) would enhance the dissolution properties of the drug. Methods: Solid dispersion of furosemide in SSG was prepared in ratios of 1:1 and 1 (furosemide):2 (SSG) by kneading method. In each case, the solid dispersion was characterized by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD) to ascertain if there were any physicochemical interactions between drug and carrier that could affect dissolution. Tablets containing the solid dispersion were formulated and their dissolution characteristics compared with commercial furosemide tablets. The dissolution studies were performed at 37 ± 0.5°C and 50 rpm in simulated gastric fluid (pH 1.2). Results: FTIR spectroscopy, DSC, and XRD showed a change in crystal structure toward an amorphous form of furosemide. Dissolution data indicated that furosemide dissolution was enhanced. XRD, DSC, FTIR spectroscopy and dissolution studies indicated that the solid dispersion formulated in 1:2 ratio showed a 5.40-fold increase in dissolution and also exhibited superior dissolution characteristics to commercial furosemide tablets. Conclusion: Solid dispersion technique can be used to improve the dissolution of furosemide