Manas Bhowmik

Effect of salts on gelation and drug release profiles of methylcellulose-based ophthalmic thermo-reversible in situ gels.

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions may be overcome by the use of thermo-reversible in situ gel. The purpose of this study was to examine the influence of different salts on the gelation, rheology and drug release of in situ gel based on methylcellulose. The gel temperature of 1% w/v methylcellulose (MC) was 60?C. It was found that 5?7% w/v sodium chloride (NaCl), 8?9% w/v potassium chloride (KCl), or 5% w/v sodium bicarbonate (NaHCO(3)) was capable of decreasing the gel temperature below physiological temperature, i.e. 37?C. Rheological studies indicated a large increase in viscosity at 37?C with the addition of salts in MC solutions. The duration of drug release from MC solution was 1.5?h. The significant observation was that the duration of drug release increased from 1.5?h to 3?5?h from salted MC solutions depending on the concentration and the type of salt. So, it can be concluded that the salted MC solutions were a better alternative than the MC solution to enhance the ocular bioavailability of the drug.

Development and in vitro evaluation of Letrozole loaded biodegradable nanoparticles for breast cancer therapy

The objectives of our study were to prepare and evaluate a biodegradable nanoparticulate system of Letrozole (LTZ) intended for breast cancer therapy. LTZ loaded poly(lactide-co-glycolide) nanoparticles (LTZ-PLGA-NPs) were prepared by emulsion-solvent evaporation method using methylene chloride and polyvinyl alcohol. Percentage of drug (with respect to polymer) was selected as formulation variable. LTZ-PLGA-NPs were characterized by particle size, zeta potential, infrared spectra, drug entrapment efficiency and in vitro release. Sonication was done with an ultrasound pulse sonicator at 70 W, 30 kHz for 90 sec to produce stable NPs of mean size range from 64 nm to 255 nm with high entrapment efficiency (68% to 82%). Percentage of drug significantly influenced particle size, entrapment efficiency and release (p <0.05). The system sustained release of LTZ significantly and further investigation could exhibit its potential usefulness in breast cancer therapy.

Effect of PEG–salt mixture on the gelation temperature and morphology of MC gel for sustained delivery of drug

Gelation temperature of MC was reduced from 59°C to 54°C with the addition of 10% PEG. Sodium tartrate (NaT) and sodium citrate (NaC) were added to the MC-PEG solution to further reduce the gelation temperature close to physiological temperature. Different techniques were used to measure the gelation temperature of all formulations. It was observed that NaC was more effective in reducing the gelation temperature of MC-PEG combination than NaT. Environmental scanning electron microscopy (ESEM) images of hydrogels containing NaC and NaT showed that NaC containing hydrogel having an interconnected microporous structure instead of the hollow rod like structure as in the case of NaT containing hydrogel. In vitro drug release studies showed that drug release time increased from 6 to 9h by only changing the type of salt from NaT to NaC in MC-PEG combination.

Effect of PVA on the gel temperature of MC and release kinetics of KT from MC based ophthalmic formulations

The effect of molecular weight of poly(vinyl alcohol) (PVA) and sodium chloride on the gelation temperature of methylcellulose (MC) was studied with the objective to develop a MC based formulation for sustained delivery of ketorolac tromethamine a model ophthalmic drug. Pure MC showed sol-gel transition at 61.2 °C. In order to reduce the gelation temperature of MC and to increase the drug release time, PVA was used. Different techniques such as test tube tilting method, UV-vis spectroscopy, viscometry and rheometry were used to measure gelation temperature of all the binary combinations of MC and PVA. It was observed that the gelation temperature of MC was reduced with the addition of 4% PVA and also the extent of reduction of the gelation temperature of MC was dependent on the molecular weight of PVA. The strong interactions between MC and PVA molecules were established using Fourier transform infrared spectroscopy. To study the in vitro drug release properties of the MC-PVA binary combinations, 6% sodium chloride was used to reduce the gelation temperature further up to physiological temperature. It was observed that the drug release time increased from 5 to 8h with the increase of molecular weight of PVA from 9×10(3) to 1.3×10(5) and this was due to the higher viscosity, better gel strength and greater interactions between the drug and PVA molecules in case of PVA (1.3×10(5)) compared to PVA (9×10(3)). In order to have an idea about the nature of interactions between the functional moieties of the drug and the polymer unit of PVA, a theoretical study was carried out.

Study of thermo-sensitive in-situ gels for ocular delivery.

The aim of the present study was the development of thermo-sensitive in-situ gels for in-vitro evaluation of ophthalmic delivery systems of ketorolac tromethamine (KT), based on methylcellulose (MC) in combination with hydroxypropylmethyl cellulose (HPMC). The gel temperature of 1% MC solution was observed at 60°C. It was found that 6% oral rehydration salt without dextrose (ORS) was capable to reduce the gel temperature below physiological temperature. HPMC was added to increase viscosity and drug release time. The results indicated a large increase in viscosity at 37°C with addition of HPMC whch provided sustained release of the drug over a 4h period. From in-vitro release studies, it could be concluded that the developed systems were thus a better alternative to conventional eye drops.

Cross-linked methyl cellulose/graphene oxide rate controlling membranes for in vitro and ex vivo permeation studies of diltiazem hydrochloride

Permeability characteristics of the anti-hypertensive drug, diltiazem hydrochloride, from uncross-linked and cross-linked methylcellulose (MC)/graphene oxide (GO) rate controlling membranes (RCMs) were investigated. The MC/GO membranes were cross-linked with different concentrations of glutaraldehyde (GLA) to examine the effect of cross-linking on the permeability characteristics. The ATR-FTIR spectra, along with solubility resistance, swelling studies, the molar mass between cross-links, and moisture absorption of cross-linked RCMs over the uncross-linked RCM confirmed the cross-linking between MC and GO. The cross sectional view of cross-linked and uncross-linked RCMs, as observed by SEM, showed that the porous and fibrillose structure of the uncross-linked RCM was disrupted after cross-linking. The cross-linked RCMs showed improved mechanical and thermal properties compared to the uncross-linked RCMs. In vitro and ex vivo drug release was found to depend on the concentration of the cross-linker, which suggests that drug delivery is controlled by the cross-link density of RCM.

Effect of gellan gum on the thermogelation property and drug release profile of Poloxamer 407 based ophthalmic formulation

The effect of gellan gum on the gelation behavior and in-vitro release of a specific drug named pilocarpine hydrochloride from different ophthalmic formulations based on poloxamer 407 is examined. The mixture of 0.3wt% gellan gum and 18wt% poloxamer (PM) solutions show a considerable increase in gel strength in physiological condition. Gel dissolution rate from PM based formulation is significantly decreased due to the addition of gellan gum. FTIR spectra analysis witnesses an interaction in between OH groups of two polymers which accounts for lowering in gelation temperature of PM-gellan gum based formulations. It is also observed from the cryo-SEM study that the pore size of PM gel decreases with an addition of gellan gum and in-vitro release studies indicate that PM-gellan gum based formulation retain drug better than the PM solution alone. Therefore, the developed formulation has the potential to be utilized as an in-situ ophthalmic drug carrier.

Attenuation of reactive nitrogen species by different flavonoids enriched fractions of Schima Wallichii

Abstract Objective To investigate Schima wallichii (S. wallichii) Choisy (Ternstroemiaceae) which is a well known plant of Sikkim in the Himalayan region, India. Methods Therefore three major flavonoid enriched fractions (FPet.Ether, FChloroform and FEthylacetate) were isolated by petroleum ether chloroform and ethyl acetate successively. The reactive nitrogen species scavenging activity of the flavonoid fractions was established using biochemical assay to measure scavenging of 2, 2 diphenyl picrylhydrazyl (DPPH), nitric oxide (NO) and peroxinitrite. Results FEthylacetate showed maximum scavenging activity: their IC50 being (7.33 ± 3.32), (7.11 ± 2.21), and (6.67 ± 2.23) μg/mL in DPPH, NO, peroxinitrite radical respectively. Presence of (57.32 ± 2.31) and (163.4 ± 2.22) μg of flavonoids and phenolic compound in 1 mg of extract is assumed to be responsible for free radical scavenging activity. Conclusion Taken together S. wallichii has potent free radical scavenging property indicating its importance in food supplement as a rich source of active flavonoid and phenolic compounds in ethyl acetate fraction which is responsible for its free radical scavenging as well as antioxidant activity.