ABSTRACT
The effect of weight average molecular weight (Mw) of methyl cellulose (MC) on the gelation behavior of Poloxamer 407 (PM) and in vitro release of Ketorolac Tromethamine (KT) from different ophthalmic formulations based on PM is examined. A drop of gelation temperature of PM is observed using MC of various M(w) by test tube tilting method, UV-vis spectroscopy, viscometry and rheometry. It is also observed that the viscosity and gel strength of all the formulations are increased with the increase in Mw of MC. PM with highest Mw of MC provides best drug release property among all the formulations. It is evident from this investigation that there is a distinct effect of M(w) of MC on the gelation behavior of PM as well as on the drug release profile of KT from PM-MC based ophthalmic formulations.
Subject(s)
Eye/drug effects , Ketorolac Tromethamine/chemistry , Methylcellulose/pharmacology , Poloxamer/chemistry , Chemistry, Pharmaceutical , Eye/pathology , Humans , Ketorolac Tromethamine/pharmacology , Methylcellulose/chemistry , Molecular Weight , Ophthalmic Solutions/chemistry , Ophthalmic Solutions/pharmacology , Poloxamer/pharmacology , Rheology , Temperature , ViscosityABSTRACT
The aim of this investigation was to develop a novel in situ gelling formulation based on poloxamer-407 (PM) for the sustained release of an ophthalmic drug. In an attempt to reduce the concentration of PM without compromising the in situ gelling capability and also to increase the drug release time, xanthan gum (XG) and guar gum (GG) were added into PM to develop different formulations. At concentrations of 18% and above, the PM was able to undergo sol-gel transition below body temperature. It was found that XG and GG at a weight ratio of 3:7 were able to convert PM solution into gel below body temperature at PM concentrations below 18%. Both the in vitro and in vivo studies indicated that the PM with an XG-GG combination had a better ability to retain the drug than PM itself. The results indicated that the developed in situ gelling formulations containing PM with XG-GG may be a better alternative than a conventional eye drop.
Subject(s)
Drug Carriers/chemistry , Galactans/chemistry , Mannans/chemistry , Ophthalmic Solutions/chemistry , Plant Gums/chemistry , Poloxamer/chemistry , Polysaccharides, Bacterial/chemistry , Drug Liberation , Gels , Rheology , Temperature , ViscosityABSTRACT
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.
Subject(s)
Citrates/pharmacology , Drug Carriers/chemistry , Gels , Methylcellulose/chemistry , Citrates/chemistry , Hydrogels/chemistry , Kinetics , Ophthalmic Solutions/chemistry , Polyethylene Glycols/pharmacology , Sodium Citrate , Tartrates/chemistry , Temperature , ViscosityABSTRACT
In this paper we reported preparation of methylcellulose-silver nanocomposite films by mixing of aqueous solution of methylcellulose with silver nitrate followed by casting. The silver nanoparticles were generated in methylcellulose matrix through reduction and stabilization by methylcellulose. The surface plasmon band at 412 nm indicated the formation of Ag nanoparticles. The MC-Ag nanocomposite films were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR). The X-ray diffraction analysis of synthesized MC-Ag nanocomposite films revealed that metallic silver was present in face centered cubic crystal structure. Average crystallite size of silver nanocrystal was 22.7 nm. The FTIR peaks of as-synthesized MC-Ag nanocomposite fully designated the strong interaction between Ag nanoparticles and MC matrix. Nano-sized silver modified methylcellulose showed enhanced mechanical properties i.e. the introduction of Ag leading to both strengthening and toughening of MC matrix. The methylcellulose-silver nanocomposite films offered excellent antimicrobial activity against various microorganisms.
Subject(s)
Anti-Infective Agents/pharmacology , Bacteria/drug effects , Metal Nanoparticles/chemistry , Methylcellulose/chemistry , Nanocomposites/chemistry , Silver Nitrate/chemistry , Anti-Infective Agents/chemical synthesis , Microscopy, Electron, Transmission , Nanocomposites/ultrastructure , Spectrophotometry, Ultraviolet , Spectroscopy, Fourier Transform Infrared , X-Ray DiffractionABSTRACT
Gelation temperature of methylcellulose (MC) can be altered by adding different additives. Pure MC showed sol-gel transition at 60°C. Sodium citrate and sodium tartrate were used alone and in combination to see the effect of individual salt and combination of salts on the gelation temperature of MC. The gelation temperature of all the binary and ternary combinations of MC and salts were measured with different methods such as test tube tilting method (TTM), UV-vis spectroscopy, viscometry, and by rheometer and also the morphology of gels were characterized with the help of environmental scanning electron microscopy (ESEM). It was observed that when 0.1 M sodium citrate (NaC) and 0.1 M sodium tartrate (NaT) were used separately, the gelation temperature of MC was reduced up to 44°C and 47°C respectively but when mixture of NaC and NaT (0.1 (M) NaC and 0.1 (M) (NaT)) were used the gelation temperature was further reduced to 36°C. It was clear from ESEM images that when NaC and NaT were used separately the formation of network was not distinguishable. But, well-connected network structure was observed when a mixture 0.1 M NaC and 0.1 M NaT was used.
Subject(s)
Citrates/chemistry , Hydrogels/chemistry , Methylcellulose/chemistry , Tartrates/chemistry , Transition Temperature , Rheology , Sodium Citrate , ViscosityABSTRACT
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.
Subject(s)
Ketorolac Tromethamine/chemistry , Methylcellulose/chemistry , Ophthalmic Solutions/chemistry , Polyvinyl Alcohol/chemistry , Temperature , Drug Carriers/chemistry , Gels , Kinetics , Models, Molecular , Molecular Conformation , Molecular Weight , Rheology , ViscosityABSTRACT
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.
