Please cite this article in press as: H. Bera, S. Kumar, Int. J. Biol. Macromol. (2017), https://doi.org/10.1016/j.ijbiomac.2017.11.019 ARTICLE IN PRESS G Model BIOMAC-8499; No. of Pages 10 International Journal of Biological Macromolecules xxx (2017) xxx–xxx Contents lists available at ScienceDirect International Journal of Biological Macromolecules journal homepage: www.elsevier.com/locate/ijbiomac Diethanolamine-modified pectin based core-shell composites as dual working gastroretentive drug-cargo Hriday Bera a,b,∗ , Sanoj Kumar b a Faculty of Pharmacy, AIMST University, Semeling, Kedah, 08100, Malaysia b Gokaraju Rangaraju College of Pharmacy, Bachupally, Hyderabad, 500090, India a r t i c l e i n f o Article history: Received 7 September 2017 Received in revised form 3 November 2017 Accepted 5 November 2017 Available online xxx Keywords: High-methoxyl pectin Alginate Fenugreek gum a b s t r a c t The current study aimed at developing diethonolamine-modified high-methoxyl pectin (DMP)-alginate (ALG) based core-shell composites for controlled intragastric delivery of metformin HCl (MFM) by com- bined approach of floating and bioadhesion. DMP with degree of amidation of 48.72% was initially accomplished and characterized by FTIR, DSC and XRD analyses. MFM-loaded core matrices were then fabricated by ionotropic gelation technique employing zinc acetate as cross-linker. The core matrices were further coated by fenugreek gum (FG)-ALG gel membrane via diffusion-controlled interfacial complexa- tion method. Various formulations demonstrated excellent drug encapsulation efficiency (DEE, 51–70%) and sustained drug eluting behavior (Q 8h , 72–96%), which were extremely influenced by polymer-blend (ALG:DMP) ratios, low density additives (olive oil/magnesium stearate) and FG-ALG coating inclusion. The drug release profile of the core-shell matrices (F-7) was best fitted in zero-order kinetic model with case- II transport driven mechanism. It also portrayed outstanding gastroretentive characteristics. Moreover, the composites were analyzed for surface morphology, drug-excipients compatibility, thermal behavior and drug crystallinity. Thus, the developed composites are appropriate for controlled stomach-specific delivery of MFM for type 2 diabetes management. © 2017 Elsevier B.V. All rights reserved. 1. Introduction During the past few decades, floating drug delivery system (FDDS) has been mooted as a frontier approach for stomach-specific drug delivery [1]. Pectin is the most commonly used matrix polymer for FDDS due to its excellent biocompatibility, high biodegradabil- ity, acid stability and suitable mechanical property. The template of pectin molecules consists primarily of linearly linked -(1-4)-d- galacturonic acid units frequently intermingled with -(1-2) linked -l-rhamnopyranose residues. The galacturonic acid units of pectin molecules are partially methylesterified [2]. The floating matrices comprising high-methoxyl (HM) pectin with a degree of methy- lation above 50% exhibit limited drug entrapment efficiency and initial burst drug elution with impaired early and long-term buoy- ancy [3]. To minimize such inconveniences, there is an unmet need to develop a suitable HM-pectin-based gastroretentive drug- cargo. Pioneering studies provided convincing evidences that the amidation of HM-pectin by diethonolamine could significantly ∗ Corresponding author at: Faculty of Pharmacy, AIMST University, Semeling, Kedah, 08100, Malaysia. E-mail address: hriday.bera1@gmail.com (H. Bera). diminish the hydrophobicity and augment the tendency to con- struct gels with superior mechanical strength [4]. In recent years, various natural biopolymers blended pectinate matrices are also being developed, which confer enhanced encapsulation efficiency and improved release characteristics of the bioactive molecules. Sodium alginate (ALG) is an anionic linear polysaccharide and often blended with pectin-based matrices to achieve desired functional properties [5]. ALG contains -1,4-linked L-glucuronic acid and - 1,4-linked D-mannuronic acid residues arranged erratically along the chains. It has a distinctive property of being instantly gelled when contacted with divalent cations (e.g., Ca +2 , Zn +2 etc.) [6]. Furthermore, pectin-based FDDS containing various low-density additives like fixed oils and magnesium stearate were reported [7]. Such low-density additives could impart buoyancy and impose a hydrophobic blockade towards the drug evading from the matrices, leading to amplified drug trapping efficiency and extended drug release behavior [1]. Unfortunately, FDDS exhibits several drawbacks. For exam- ple, the performance of low-density floating systems is extremely dependent on the filling state of the stomach that would modu- late the gastric emptying process [8]. Recently, a flurry of scientific investigations has employed a mucoadhesive biopolymeric coating on floatable systems, which could improve gastroretention capa- https://doi.org/10.1016/j.ijbiomac.2017.11.019 0141-8130/© 2017 Elsevier B.V. All rights reserved.