International Journal of Biological Macromolecules 70 (2014) 1–9 Contents lists available at ScienceDirect International Journal of Biological Macromolecules j ourna l h o mepa ge: www.elsevier.com/locate/ijbiomac Hydrolyzed polyacrylamide grafted maize starch based microbeads: Application in pH responsive drug delivery C. Mallikarjuna Setty a , Anand S. Deshmukh b,∗ , Aravind M. Badiger c a Department of Pharmaceutics, The Oxford College of Pharmacy, 6/9, 1st cross Begur Road, Hongasandra, Bangalore 560068, India b Department of Pharmaceutics, Shree Dhanvantary Pharmacy College, Kim, Kudsad Road, Surat, Gujarat 394110, India c BDR Pharmaceuticals International Private Limited, Vadodara, Gujarat 390 001, India a r t i c l e i n f o Article history: Received 28 April 2014 Received in revised form 30 May 2014 Accepted 11 June 2014 Available online 24 June 2014 Keywords: Starch graft copolymer Microwave assisted grafting pH responsive microbeads a b s t r a c t The present study details the synthesis, characterization and pharmaceutical application of hydrolysed polyacrylamide grafted maize starch (HPam-g-MS) as promising polymeric material for the develop- ment of pH responsive microbeads. Different grades of graft copolymer were synthesized by changing the net microwave irradiation time, while keeping all other factors constant. Acute oral toxicity study performed in rodents ensured the bio-safety of graft copolymer for clinical application. Various batches of aceclofenac loaded microbeads were prepared by ionic gelation method using synthesized graft copoly- mers and evaluated for formulation parameters. FTIR spectroscopy confirmed the chemical compatibility between drug and graft copolymer. Results of in vitro release study (USP type-II) carried out in two dif- ferent pH media (pH 1.2 acid buffer and pH 7.4 phosphate buffer) showed that release rate of drug from developed microbeads was a function of both: (a) surrounding pH and (b) the matrix composition. The drug release was relatively higher at alkaline pH as compared to acidic pH and this feature is desirable from viewpoint of site specific drug delivery. A direct correlation was observed between percentage grafting and microbeads performance and it presents a scope for further research on application and optimization of HPam-g-MS based microbeads as drug delivery carriers. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Along the entire length of human gastrointestinal tract (GI tract), pH varies widely i.e. acidic in stomach to alkaline in the lower part of intestine. Exploitation of this differing pH (as a trigger) at vari- ous locations of GI tract using stimuli responsive polymeric carrier (intelligent material) has become one of the major strategies in the design and development of site specific drug delivery system. In other words, this type of delivery system can release enclosed drug from the matrix more specifically at predetermined site (such as at alkaline pH of intestine while avoiding/minimizing release in stomach) at desirable rate under predetermined conditions [1]. Native starch irrespective of its source is undesirable for many pharmaceutical applications due to its inability to withstand var- ious processing conditions such as extreme temperature, diverse ∗ Corresponding author at: Department of Pharmaceutics, Shree Dhanvantary Pharmacy College, Near Kim Railway Station, Kudsad Road, Kim (E), Surat, Gujarat 394110, India. Tel.: +91 9726609206; fax: +91 2621231077. E-mail addresses: anand4ds@rediffmail.com, anand4ds@yahoo.co.in (A.S. Deshmukh). pH, high shear rate, and freeze thaw variations. To overcome this, chemical modification of starch such as etherification, esterifica- tion, cross linking, oxidation, cationization and grafting are usually done. It incorporates unique physicochemical and functional char- acteristics into starch molecules, making it suitable (as promising polymeric material) for diverse applications [2,3]. Among various types of chemical modification, grafting of polyacrylamide chains on the backbone of starch is quite simple and economic. Both con- ventional [4,5] and microwave assisted [6,7] grafting techniques are reported. Comparatively, grafting with the help of microwave radiation is cleaner, straightforward, eco-friendly and highly reproducible technology which conforms to all the accepted norms of green chemistry. Further in case of microwave irradiation based method, the process is very simple and if all other factors (wattage of radi- ation, polysaccharide concentration and monomer concentration) are kept constant, then the percentage grafting can be precisely controlled in terms of net irradiation time, which being regulated electronically by the inbuilt digital timer of the microwave oven, tends to be highly accurate and reproducible [1,8]. From experi- mental viewpoint, our intention is to take the advantage of this fact for the synthesis of different matrix compositions (percentage http://dx.doi.org/10.1016/j.ijbiomac.2014.06.027 0141-8130/© 2014 Elsevier B.V. All rights reserved.