ORIGINAL ARTICLE e-ISSN: 2349-0659 p-ISSN; 2350-0964 Formulation Development, Optimization, and Characterization of Cilnidipine-Loaded Self-microemulsifying Drug Delivery System Kumar Anand 1 , Samit Karmakar 2 *, Pallab Mandal 1 , Md. Adil Shaharyar 1 , Rudranil Bhowmik 1 , Avishek Mondal 1 , Subhabrata Ray 3 , Sanmoy Karmakar 1 * A BSTRACT Cilnidipine, a 2, 4-dihydropyridine antihypertensive, is poorly bioavailable and belongs to Biopharmaceutical Classifcation System Class II. The present study was carried out to develop and evaluate a cilnidipine-loaded self-microemulsifying drug delivery system (SMEDDS) using food grade oil for enhanced pharmacokinetic parameters. The SMEDDS was prepared by low-energy method. A pseudo-ternary phase diagram was developed using triacetin, Tween 20, and Transcutol HP as oil, surfactants, and cosurfactants, respectively. The statistically optimized formulation was obtained and was evaluated for relevant in vitro characterizations. Globule size, zeta potential, and polydispersity index (PDI) of the optimized formulation were found to be 9.045 nm, −2.32 mv and 0.203, respectively, indicating stable and uniformly distributed microemulsion nature of the formulation. Developed SMEDDS of viscosity 31 cps was found to be clear in 500 times dilution in water and phosphate bufer pH 1.2. Selection of the optimized SMEDDS was followed by various formulation characteristics, including goat intestinal membrane permeability. The in vitro dissolution study of optimized SMEDDS exhibited much better result as compared to the marketed tablet of cilnidipine. Keywords: Biopharmaceutical classifcation system Class II, Cilnidipine, Design expert, Goat intestinal membrane permeability, Pseudo- ternary phase diagram, Self-microemulsifying drug delivery system Asian Pac. J. Health Sci., (2021); DOI: 10.21276/apjhs.2021.9.1.05 ©2021 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/ licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. I NTRODUCTION Drugs falling under Biopharmaceutical Classifcation System (BCS) Class II and IV are known to have very low absorption, which is difcult to overcome using conventional dosage forms. Accordingly, lipoidal drug delivery systems might become helpful to overcome the above-mentioned constraints and may achieve desired clinical benefts at a lower dose with the added advantage of reduced toxicities. Cilnidipine is one of the recently approved drugs entity for better antihypertensive management in comparison to other calcium channel blockers. [1] In the present study, self-microemulsifying drug delivery system (SMEDDS) of cilnidipine, a newer congener with problems characteristic of the BCS Class II group, was developed, investigated, and evaluated. SMEDDS, a novel drug delivery system, is an isotropic mixture of oil, surfactant, cosurfactant, and drug. SMEDDS has the ability to form oil-in-water (O/W) microemulsion in a spontaneous manner under mild agitation in gastrointestinal tract fuids after oral administration. Enhancement in the solubility and permeability of the BCS Class II drugs, spontaneous formation, thermodynamic stability, improved bioavailability, and feasibility of the preparation are among the primary advantages of SMEDDS. [2] Here, the presence of triglyceride in composition of self-microemulsifying pre-concentrate is expected to enhance the bioavailability by improving lymphatic transport bypassing the portal circulation, which provides a greater interfacial area for absorption and improvement of the physical and chemical stability of drugs. [3,4] M ATERIALS AND M ETHODS Chemical Reagent Triacetin (glycerol triacetate) and diethylene glycol monoethyl ether (Transcutol HP) were purchased from Sigma-Aldrich. Tween 20, Tween 80, and Span 80 were purchased from Merck Millipore. 1 Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India, 2 Medical College, Kolkata, West Bengal, India, 3 Dr. B. C. Roy College of Pharmacy and Allied Health Sciences, Dr. Meghnad Saha Sarani, Durgapur, West Bengal, India CorrespondingAuthor:SanmoyKarmakar,DepartmentofPharmaceutical Technology, Director, Bio-Equivalence Study Centre, Jadavpur University, Kolkata, West Bengal, India. E-mail: sanmoykarmakar@gmail.com Samit Karmakar, Medical College, Kolkata, West Bengal, India. E-mail: samitkarmakar2015@gmail.com How to cite this article: Anand K, Mandal P, Shaharyar MA, Bhowmik R, Mondal A, Ray S, Karmakar S. Formulation Development, Optimization, and Characterization of Cilnidipine Loaded Self-microemulsifying Drug Delivery System. Asian Pac. J. Health Sci., 2021;9(1):23-29. Source of support: Nil Conficts of interest: None. Received: 13/08/21 Revised: 29/09/21 Accepted: 17/10/21 Labrasol was a gift sample from Gattefosse, India. Analytical grade sodium dodecyl sulfate (SDS) was purchased from E-Merck, India. Glycerol, isopropyl alcohol, and PEG 400 were purchased from Merck, India. Cilnidipine was a gift from PURE CHEM PVT. LTD., Gujarat, India, lercanidipine, α-napthol, and ketoconazole were obtained as a gift sample. All chemicals used were of analytical grade. Milli-Q water was used for the present study. Methods Selection of oil Selection of oil for the formulation of cilnidipine was done on the basis of solubility of the cilnidipine in various oils. Oil, safe for chronic use, and low cost was also a concern. Hence, solubility of cilnidipine was determined in various oils (olive oil, almond oil, castor oil, triacetin, sesame oil, faxseed oil, rice bran oil, and Capmul MCM).