Vol.:(0123456789) 1 3 J Incl Phenom Macrocycl Chem DOI 10.1007/s10847-017-0747-z ORIGINAL ARTICLE Formulation and evaluation of gel containing nanostructured lipid carriers of tretinoin–Epi-β-CD binary complex for topical delivery Bina Gidwani 1  · Piyush Jaiswal 1  · Amber Vyas 1   Received: 1 October 2016 / Accepted: 23 August 2017 © Springer Science+Business Media B.V. 2017 Introduction Nanostructured lipid carriers (NLCs) are the second gen- eration nanoparticles after solid lipid nanoparticles (SLN). They possess highly unordered matrix that shows great imperfections in the crystal lattice and leaves enough space to accommodate drug molecules, leading to improved drug loading and modulation of drug release [1, 2]. In recent years, NLCs have been used in topical drug formulations and cosmetic products due to their nano size range that ensures close contact to the stratum corneum while the lipid layer provides selective drug delivery to skin [3, 4]. They have unique advantage of providing sustained/controlled/pro- longed drug release there by reducing the side efects [5]. Retinoids are considered to be the frst line treatment for treatment of mild to moderate forms of acne [6]. Tretinoin (all trans retinoic acid) is a non aromatic derivative product from vitamin A which has been widely used in the treat- ment of various skin disorders like acne, psoriasis, photo- ageing which involve cell diferentiation, proliferation and infammation of cells [7–9]. But its extensive use has been reduced due to its adverse side efects and low bioavailabil- ity [10]. Despite this, the poor aqueous solubility and weaker photostability are associated technical drawbacks [11]. All these issues led us to search for an improvement in topical delivery of tretinoin by inclusion with cyclodextrins (CDs). Literature reports enormous study about complexation on the release of drugs designed for topical use [12] like in a study the enhanced release of drug betamethasone from pre- pared topical formulation i.e. ointment containing β (beta) and γ (gamma) cyclodextrin complexes. The major role of cyclodextrins in topical drug delivery lies in the enhance- ment of drug release and permeation; reduced dosing; drug stabilization; reduction of the adverse efects, bioconversion Abstract The objective of present research work was to formulate and evaluate topical gel containing treti- noin–cyclodextrin (CD) binary complex loaded into nano- structured lipid carriers (NLCs). Use of cyclodextrin and nanolipid carrier together in a system produced a synergistic efect by increasing the drug release and skin permeation, thus improving the overall therapeutic efect. Two difer- ent cyclodextrins i.e. β-CD and its water soluble polymeric derivative epichlorohydrin-β-cyclodextrin (EPI-β-CD) were used to obtain binary inclusion complex of drug-cyclodex- trin (D-CD) systems by two diferent techniques (kneading and co-evaporation). The prepared solid complexes were characterized by FTIR, DSC, XRD etc. and the best system was selected for loading into nanolipid carriers. NLC com- prising glyceryl mono stearate (GMS) and oleic acid were obtained by slightly modifed emulsifcation evaporation method. Four diferent formulations of NLCs were suitabil- ity characterized for particle size, zeta potential, entrapment efciency, drug loading and drug release. EPI-β-CD was found to be more efective than β-CD in enhancing solubility and dissolution properties of tretinoin. The most efective NLC formulation was incorporated into carbopol hydrogel which showed better permeation properties than that of the reference gel (0.1%). Keywords Tretinoin · Nanostructured lipid carriers · β-Cyclodextrin · Epichlorohydrin-β-cyclodextrin · Hydrogel · Skin permeation * Amber Vyas ambervyas@gmail.com; beenagidwani@gmail.com 1 University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, C.G. 492 010, India