In vivo, In vitro Evaluation of Linseed Mucilage Based Buccal Mucoadhesive Microspheres of Venlafaxine

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 to F4 (1 to 2.5percent) 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 plus minus 1.35percent, 92.10 plus minus 1.37percent incorporation efficiency, highest swelling index 0.770 plus minus 1.23. F4 showed a marked increase in the bioavailability after buccal administration (51.86 plus minus 3.95) as compared to oral route (39.60 plus minus 6.16). Also it took less time to reach maximum plasma concentration of 21.38 plus minus 1.05 ng/ml as compared to oral solution where it required 180 min to reach maximum plasma concentration of 17.98 plus minus 1.14. It is concluded from the results that linseed mucilage can be used in the production of the mucoadhesive microspheres. (Authors abstract)

Microspheres find a unique place in the field of bioadhesive drug delivery systems. Bioadhesive microspheres for the gastro intestinal tract, nasal route, and for the oral cavity are reported in the literature. Buccal mucoadhesive microspheres have several advantages such as ease of removal, ease of application, less irritation due to less surface area in contact with mucosal membrane, and also the presence of mucous, finally controlled release of drug aids in almost absorption of all drug due to the highly permeable buccal membrane. The aim of this study was to investigate the mucoadhesive potential of linseed mucilage and formulation, and in vivo evaluation of venlafaxine buccal mucoadhesive microspheres to improve bioavailability by avoiding hepatic first pass effect. The literature revealed that the yield of mucilage in basic PH and at higher temperature is maximum, therefore the 85°C boiling temperature of the solution was considered maximum. Ethyl alcohol, methanol, and acetone were tried for precipitation.
Yield of extract precipitated with ethyl alcohol was 8percent, whereas yield of extract precipitated with methanol and acetone were 7percent and 6.5percent, respectively. Production yield was found in the range of 37–44percent. The yield of the microspheres was increased when the mucilage ratio was increased. Other variables that were assessed and described in this study included: Drug loading and incorporation efficiency; Swelling property; Ex vivo mucoadhesion studies; In vitro drug release study/ex vivo drug permeation study using buccal sheep mucosa;  Drug release kinetics;  Mechanism of drug release; Scanning electron microscopy (SEM); Differential scanning calorimetry (DSC); Xray diffraction study; Fourier Transform Infrared spectroscopic study FTIR); Stability of the microspheres.

Histological assessment showed that no change in mucosal structure of control mucosa (formulation untreated buccal mucosa) stained with hematoxylin eosin and the test mucosa (formulation treated buccal mucosa). This confirms that the microspheres can be applied to the buccal mucosa without irritation or any damage to buccal mucosa.

The  results demonstrated that spray drying is a suitable technique for preparation of buccal mucoadhesive microspheres of venlafaxine based on linseed mucilage. In vivo results showed that there is remarkable increase in the bioavailability when venlafaxine was administered in the form of buccal mucoadhesive microspheres. Based on all in vivo and in vitro results, this study concluded that the mucoadhesive microspheres based on linseed mucilage might be considered as a promising buccal mucoadhesive delivery system for the administration of venlafaxine. The linseed mucilage can be used as a very good mucoadhesive agent and can be explored as a novel mucoadhesive agent. (Editors comments)