ABSTRACT
Linseed is the crop that is used as a foodstuff in European and Asian countries. The objective of the present work was to extract mucilage from linseed, utilize it as mucoadhesive gelling agent along with synthetic polymers and administration of venlafaxine by buccal route in the gel form. Buccal administration of venlafaxine will avoid first pass metabolism, which will increase the bioavailability of the drug. Linseed mucilage based buccal mucoadhesive gel preparations in combination with chitosan, carbopol 934P, carboxy methylcellulose and polyvinyl pyrrolidone were formulated and the viscosity, gel strength, percentage mucoadhesion and in vitro diffusion of the formulation was evaluated. Formulation (F2) was subjected to in vivo analysis in rabbits. Formulation F2, which contained linseed mucilage (2 %) and chitosan (0.5 %), showed the highest percentage of mucoadhesion, gel strength and sustained drug diffusion. The bioavailability by the oral route and buccal route were compared with that of the intravenous route. The bioavailability of venlafaxine in the formulation F2 was 63.08 ± 1.28 % by buccal route, which was higher than by the oral route (39.21 ± 6.18 %). Based on these results, the combination of linseed mucilage and chitosan can be used to form a buccal mucoadhesive gel and increase the bioavailability of venlafaxine.
Subject(s)
Adhesives/administration & dosage , Cyclohexanols/administration & dosage , Drug Delivery Systems/methods , Flax , Mouth Mucosa/drug effects , Seeds , Adhesives/metabolism , Administration, Buccal , Administration, Oral , Animals , Cross-Over Studies , Cyclohexanols/metabolism , Drug Evaluation, Preclinical/methods , Flax/metabolism , Gels , Mouth Mucosa/metabolism , Rabbits , Sheep , Venlafaxine HydrochlorideABSTRACT
Venlafaxine is a newer antipsychotic drug which shows first pass effect. Cress seed is also called as garden cress or green salad. This study examined the mechanical (gel strength, adhesiveness) and rheological properties of cress seed mucilage based gels that contain different ratios of carbopol 934 P (0.5-1.5%). In addition, diffusion of venlafaxine from gel formulations was evaluated. The selected formulation was further analyzed for pharmacokinetic parameters in rabbits. All formulations exhibited pseudoplastic flow with thixotropy. Formulation F5 showed the C(max) of 24.19 ± 0.72 ng/ml by buccal route of administration and 17.98 ± 1.15 ng/ml by oral route of administration. The bioavailability of F5 by buccal route was 54.44% and that of by oral route was 39.60%. A combination of the cress seed mucilage and carbopol 934 P resulted in a prolonged and higher venlafaxine delivery by buccal route of administration.
Subject(s)
Cyclohexanols/pharmacology , Gels , Selective Serotonin Reuptake Inhibitors/pharmacology , Cyclohexanols/chemistry , In Vitro Techniques , Selective Serotonin Reuptake Inhibitors/chemistry , Venlafaxine Hydrochloride , ViscosityABSTRACT
The objective of present work was to enhance the solubility and bioavailability of poorly aqueous soluble drug Irbesartan (IBS). The solid dispersions were prepared by spray drying method using low viscosity grade HPMC E5LV. Prepared solid dispersions were characterized by dissolution study, fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction studies (XRD). Results of the SEM, DSC and XRD study showed the conversion of crystalline form of IBS to amorphous form. The dissolution rate was remarkably increased in case of solid dispersion compared to pure IBS. Solubility and stability of solid dispersion was increased due to surfactant and wetting property, slowing devitrification and having anti-plasticization effect of HPMC E5LV. In vivo studies were performed in healthy rabbits (New Zealand grey) and compared with plain IBS. Solid dispersions showed increase in relative bioavailability than the plain IBS suspension. In conclusion, the prepared solid dispersions showed remarkable increase in solubility, dissolution rate and hence bioavailability of poorly water soluble drug Irbesartan.
Subject(s)
Biphenyl Compounds/chemistry , Tetrazoles/chemistry , Animals , Biological Availability , Biphenyl Compounds/pharmacokinetics , Calorimetry, Differential Scanning , Crystallization , Irbesartan , Rabbits , Solubility , Spectroscopy, Fourier Transform Infrared , Tetrazoles/pharmacokinetics , Viscosity , X-Ray DiffractionABSTRACT
The purpose of the present research work was to extract linseed mucilage, use it as a mucoadhesive agent and to develop mucoadhesive microspheres for buccal delivery with an intention to avoid hepatic first-pass metabolism, by enhancing residence time in the buccal cavity. Linseed mucilage was extracted and used to prepare microspheres with varying concentrations of mucilage from formulation F1-F4 (1-2.5%) by spray-drying technique. The microspheres were evaluated for the yield, particle size, incorporation efficiency, swelling property, in vitro mucoadhesion, in vitro drug release, histological study, and stability. Microspheres were characterized by differential scanning colorimetry, scanning electron microscopy, and X-ray diffraction study. Further, the bioavailability study using the New Zealand rabbits was carried out. Formulation F4 showed the maximum mucoadhesion 89.37 ± 1.35%, 92.10 ± 1.37% incorporation efficiency, highest swelling index 0.770 ± 1.23. F4 showed a marked increase in the bioavailability after buccal administration (51.86 ± 3.95) as compared to oral route (39.60 ± 6.16). Also it took less time to reach maximum plasma concentration of 21.38 ± 1.05 ng/ml as compared to oral solution where it required 180 min to reach maximum plasma concentration of 17.98 ± 1.14. It is concluded from the results that linseed mucilage can be used in the production of the mucoadhesive microspheres.
