Interpenetrating polymer network of locust bean gum-poly (vinyl alcohol) for controlled release drug delivery

Abstract

A novel interpenetrating polymer network (IPN) microspheres of locust bean gum (LBG) and poly (vinyl alcohol) (PVA) was developed for oral controlled release of buflomedil hydrochloride (BH) by emulsion crosslinking method using glutaraldehyde as crosslinker. The effects of gum–polymer ratio, concentration of crosslinker and internal phase viscosity were evaluated thoroughly. Drug entrapment efficiency, particle size distribution, swelling property and in vitro release characteristics with kinetic modelling of microspheres were evaluated. The microspheres were characterised by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), solid state C¹³ NMR, X-ray diffraction study (XRD) and differential scanning colorimetry (DSC). The microspheres showed control release property without showing any incompatibility in IPN device. Hence, IPN microspheres of LBG and PVA can be used as a potential carrier for controlled oral delivery of highly water soluble drugs like BH.

Introduction

Drug delivery research is primarily focussed on targeted delivery of the drug to the desired organ system to minimise toxicity and maximise therapeutic efficacy. As oral route is the most popular route of administration, a large emphasis is given on the development of controlled oral drug delivery systems. Drug substances with high water solubility and short half life (elimination half-life 2–3 h) get readily absorbed and eliminated, thus requiring frequent dosing (Alavijeh, Chishty, Qaiser, & Palmer, 2005). This may lead to decrease in patient compliance and increase chances of side effects due to dose dumping (Phutane et al., 2010, Ray et al., 2010). Thus, the drugs having high water solubility and short half-life warrants extensive research to reduce frequent dosing and dose related side effects by controlling their release rate. Fabrications of drug delivery devices like micropaticles or nanospheres are some of the approaches to control the release of highly water soluble drugs. Recently researchers has given a strong emphasis on natural polymer based approaches to develop controlled drug delivery systems. The use of synthetic polymers for drug delivery purposes is of limited application due to problems in biodegradability, use of organic solvents resulting in environmental pollution etc. (Halder, Mukherjee, & Sa, 2005). However natural polymers are considered to be much safer since organic solvents are not required for their processing and they are biodegradable in nature (Vijan et al., 2012, Vyas and Khar, 2002). A lot of natural gums like alginate (Das and Senapati, 2008, Yegin et al., 2007), chitosan (Win, Shin-ya, Hong, & Kajiuchi, 2003), guar gum (Thimma and Tammishetti, 2001), xanthan gum (Ray, Maiti, & Sa, 2008) have been extensively studied for the fabrication of drug delivery systems. However, the use of these gums has their own problems like uncontrolled swelling and premature release of loaded drug. The concept of polymeric blend microsphere is quite effective in overcoming the above problems. Interpenetrating polymer network (IPN) is one such formulation which is considered to be promising in delivery of bioactive molecules, particularly in controlled release applications (Changez, Burugapalli, Koul, & Chowdary, 2003). An IPN is a composite of two polymers, which is obtained when at least one polymer network is synthesised or cross-linked independently in the immediate presence of the other. Recently a large number of IPN microspheres have been developed (Agnihotri and Aminabhavi, 2005, Ray et al., 2010, Soppimath et al., 2000). Poly (vinyl alcohol) (PVA) based IPN systems are extensively studied due to its inherent non-toxicity, non-carcinogenicity, biocompatibility and desirable physical properties such as rubbery or elastic nature and high degree of swelling in aqueous solution leading to its extensive industrial use. Chemical crosslinking between these polymers provides improved mechanical properties and thermal stability (Mishra, Bajpai, Katare, & Bajpai, 2006).

In this present study, screening of a new PVA based natural polysaccharide IPN system has been focussed. Locust bean gum (LBG), a natural polysaccharide, was chosen for the study. Locust bean gum is a high molecular weight branch polysaccharide and is extracted from the seeds of carob tree Ceratonia siliqua. It consists of a (1,4)-linked β-d-mannopyranose backbone with branch points from their 6-positions linked to α-d-galactose (1,6-linked α-d-galactopyranose. The molecular weight of LBG is 300,000–360,000. It is less soluble in water and needs heating to dissolve. Being non-ionic, it is not affected by pH or ionic strength. It is dispersible in either hot or cold water, forming a sol having a pH of 5.4–7.0, which may be converted to a gel by the addition of small amounts of sodium borate. Previously, we have reported ion crosslinked hydrogel beads of carboxymethyl LBG for controlled oral delivery of glipizide (Maiti et al., 2010). Recently we have developed IPN hydrogel microspheres composed of sodium carboxymethyl cellulose and PVA to encapsulate diclofenac sodium (Banerjee et al., 2012). In continuation to the above works, IPN hydogel microspheres of locust bean gum and poly (vinyl alcohol) has been prepared and further characterised by FT-IR, SEM, XRD and DSC. An attempt was made to prepare an IPN hydrogel microsphere by using locust bean gum and PVA for oral controlled delivery of buflomedil hydrochloride (BH). Buflomedil is readily absorbed in the gastrointestinal tract and has a plasma half-life of approximately 2–3 h. Pharmacologically, buflomedil increases perfusion to impaired vascular beds of the microcirculation, increases arterial perfusion with minimal effects on central haemodynamics, exhibits apparent oxygen “sparing” effects in animal experiments, demonstrates inhibitory effects on platelet aggregation, and, in preliminary experiments, appears to improve deformability of erythrocytes with abnormal fluidity. A non-specific α receptor blocking activity appears to be involved, at least in part, in these pharmacologic effects (Dubourg & Scamuffa, 1981).