Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces journal homepage: www.elsevier.com/locate/colsurfb Bioadhesive polymeric film-based integrative platform for the unidirectional carbamazepine release from a volatile microemulsion Sachin Rathod a , Rahul Tripathi b , Gunjan Verma c , Vinod K. Aswal d , Pratap Bahadur e , Sanjay Tiwari a, ⁎ a UKA Tarsadia University, Maliba Pharmacy College, Gopal-Vidyanagar Campus, Surat, 394350, Gujarat, India b PERD Centre, Ahmedabad, 380054, Gujarat, India c Chemistry Division, Bhabha Atomic Research Centre, Mumbai, 400085, India d Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai, 400085, India e Chemistry Department, Veer Narmad South Gujarat University, Surat, 395007, Gujarat, India ARTICLE INFO Keywords: Bioadhesive film Carbamazepine Pseudo-ternary system Sustained drug release Microemulsion Solvent casting ABSTRACT Carbamazepine (CBZ) shows inconsistent absorption primarily due to its poor dissolution rate. In this study, we describe a bioadhesive polymeric film, embedded with microemulsion (ME), as a tool to enable improved CBZ dissolution and achieve sustained release. The ME was formulated using pseudo-ternary components; water, oil (n-butyl acetate), surfactant (tocopheryl polyethylene glycol 1000 succinate, TPGS) and cosurfactant (1,4-bu- tanediol). The region at surfactant to co-surfactant ratio of 1:1 was characterized using dynamic light scattering, small angle neutron scattering and differential scanning calorimetry. Scattering studies showed that size dis- tribution did not change upon water addition and temperature. Optimized ME composition containing CBZ was embedded into bioadhesive films composed with a backing layer. We successfully demonstrate the confinement of CBZ-ME into the film matrix and thereupon, the achievement of unidirectional sustained drug release up to 8 h. Our further investigations are directed over testing the system for localized drug delivery applications. 1. Introduction Carbamazepine (CBZ) is used in first line pharmacological treatment of trigeminal neuralgia [1]. Despite high intestinal permeability, the bioavailability of CBZ is inconsistent primarily due to its poor dissolu- tion-rate and limited absorption [2]. Compensatory high oral dose ad- ministration (400–1200 mg/day) results into serious side effects, in- terrupted treatment and overall treatment failure [1]. A variety of particle engineering approaches have been explored to improve its dissolution rate [3–5]. Typically, nanoparticle matrices are prepared through emulsification of volatile organic phase, containing the drug and carrier, with aqueous stabilizer system. Nanoparticles are formed following the evaporation of organic phase. However, average size of resulting nanoparticles is typically more than 100 nm [6,7]. Alter- natively, high-shear forces are employed for nano-milling of drug par- ticles. Still, complex manufacturing, changes in drug crystallinity and limited dispersion stability of reconstituted nanoparticles remain a formidable challenge in the milling process [3,8]. Microemulsions (MEs), being spontaneously assembled nano-dro- plets (< 50 nm), present high dispersion stability with insignificant energy investment [9]. Considering their easy and inexpensive pro- duction approach, MEs have received widespread acceptance among formulation scientists for achieving improved solubilization and per- meation of poorly water soluble drugs [10–12]. In accord to the com- position of water, oil and surfactants, the system enables achieving a rich variety of self-assembled microstructures. Interestingly, solubili- zation of CBZ has shown to affect the curvatures of microstructures and the transition points between different phases [13]. In addition, the formulations with solubilized CBZ have shown improved partitioning and drug transport across the Caco-2 cells, without interfering with the barrier integrity [14]. At the same time, MEs have been exploited to prepare water-dis- persible drug nanoparticles using ‘all solvent removal’ approach [12,15]. Essentially, the technique involves inclusion of volatile oil and co-surfactant (CoS) into the system which can directly be converted to nanoparticles through spray drying or lyophilization [12,16]. In this study, we present an integrated platform composed of vola- tile CBZ-microemulsion embedded into a buccal bioadhesive film composed of sodium alginate and carboxymethyl cellulose; biocompa- tible, pharmaceutically acceptable polymers. The film was backed with https://doi.org/10.1016/j.colsurfb.2018.07.009 Received 17 March 2018; Received in revised form 12 May 2018; Accepted 4 July 2018 ⁎ Corresponding author. E-mail address: tiwarisanju@gmail.com (S. Tiwari). Colloids and Surfaces B: Biointerfaces 170 (2018) 683–691 Available online 05 July 2018 0927-7765/ © 2018 Elsevier B.V. All rights reserved. T