Interpenetrating polymer network of locust bean gum-poly (vinyl alcohol) for controlled release drug delivery
Highlights
► No IPN microsphere system was developed by using LBG before this. ► This microsphere showed pH responsive release characteristics. ► Detailed in vitro characterizations of the IPN microspheres were evaluated. ► Particles showed zero order release.
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).
Section snippets
Materials
Buflomedil hydrochloride was obtained as gift sample from Fresenius Kabi Oncology Limited (Kalyani, West Bengal, India). Locust bean gum (Molecular weight 310,000) was supplied by Hindustan Gums (Hariyana, India). Poly(vinyl alcohol) (PVA: 98% hydrolysed, average molecular weight 125,000), light liquid paraffin (LLP, viscosity 25–80 mPa at 20 °C) was procured from HiMedia Laboratories Private Limited (Mumbai, India). Span 80 was procured from Pioneer in-organics (Delhi, India). Hydrochloric acid
Formation of microsphere
In the present study, we have prepared the interpenetrating polymer network hydrogel microsphere by emulsion crosslinking method using gluteraldehyde as a crosslinker. Being a natural polysaccharide, LBG has an inherent property to swell in presence of water. But this swelling behaviour is abrupt. To control this abrupt swelling property, we have crosslinked native gum and PVA by GA. The crosslinker, GA, is a bi-functional crosslinker and help to form the three dimensional polymer networks.
Conclusion
The IPN microspheres of PVA and LBG was successfully prepared using GA as a crosslinker for encapsulating buflomedil hydrochloride having short elimination half life (2–3 h). The IPN microsphere showed extended release profile following zero order release kinetic. The release of drug was highly depeendent on the IPN blend ratio, crosslinker amount and percentage drug loading. The FT-IR study confirmed the stability of drug in formulation and also confirmed the formation of IPN matrix. The NMR
Conflict of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
Acknowledgements
Santanu Kaity is thankful to CSIR, New Delhi for financial support as CSIR – SRF [Grant No. 09/554(0029)/2011. EMR-I]. The authors are thankful to Fresenius Kabi Oncology Limited (Kalyani, West Bengal, India) for supplying the gift sample of buflomedil hydrochloride. The authors are also thankful to Hindustan Gums (Hariyana, India) for supplying LBG as a gift sample. The authors are thankful to Bioequivalence Study Centre, Jadavpur University (India) for particle size analysis, CIF, BIT-Mesra
References (35)
- et al.
Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery
NeuroRx: The Journal of the American Society for Experimental NeuroTherapeutics
(2005) - et al.
Interpenetrating polymer network (IPN) hydrogel microspheres for oral controlled release application
International Journal of Biological Macromolecules
(2012) - et al.
The effect of composition of poly(acrylic acid) – gelatin hydrogel on gentamicin sulphate release: In vitro
Biomaterials
(2003) Rate of release of medicaments from ointment bases containing drugs in suspension
Journal of Pharmaceutical Sciences.
(1961)- et al.
Characterization of poly(vinyl alcohol)/poly(ethylene glycol) hydrogels and PVA-derived hybrids by small-angle X-ray scattering and FTIR spectroscopy
Polymer
(2004) - et al.
Interactions between locust bean gum and cellulose characterized by 13C NMR spectroscopy
Carbohydrate Polymers
(1998) - et al.
In vitro evaluation of novel sustained release microspheres of glipizide prepared by the emulsion solvent diffusion-evaporation method
Journal of Young Pharmacists
(2010) - et al.
A simple equation for description of solute release II. Fickian and anomalous release from swellable devices
Journal of Controlled Release
(1987) - et al.
Microwave assisted synthesis and characterization of acrylamide grafted gellan, application in drug delivery
Carbohydrate Polymers
(2012) - et al.
Carbon transformations during decomposition of different components of plant leaves in soil
Soil Biology and Biochemistry
(2000)
Formulation and characterization of pH sensitive drug carrier based on phosphorylated chitosan (PCS)
Carbohydrate Polymers
CP/MAS 13C NMR analysis of the structure and hydrogen bonding of melt-crystallized poly(vinyl alcohol) films
Polymer
Development of novel interpenetrating network gellan gum-poly(vinyl alcohol) hydrogel microspheres for the controlled release of carvedilol
Drug Development and Industrial Pharmacy
Stearic acid-coated chitosan-based interpenetrating polymer network microspheres: Controlled release characteristics
Indusstrial Engineering and Chemistry Research.
Investigation on crosslinking density for development of novel interpenetrating polymer network (IPN) based formulation
Journal of Scientific and Industrial Research
Synthesis and characterization of poly(acrylic acid)/modified bentonite superabsorbent polymer
International Journal of Polymeric Materials
Differential scanning calorimetry in life science: Thermodynamics, stability, molecular recognition and application in drug design
Current Medicinal Chemistry
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