• TEJASWINI MANE Department of Pharmaceutical Quality Assurance, Dr. D. Y. Patil College of Pharmacy, Pune, Maharashtra, India.
  • MUKESH MOHITE Department of Pharmaceutical Quality Assurance, Dr. D. Y. Patil College of Pharmacy, Pune, Maharashtra, India.



Apremilast, Saccharin, Cocrystal, Solvent Evaporation, Solubility, Factorial Design, Topical gel


Objective: Most of the drugs are relevant BSC class II and class IV having solubility problem. Co-crystallization of drug with coformer is an immense approach used to explore the physicochemical properties of drug. The objective of the present work was to design formulate and evaluate the drug cocrystals of poorly soluble drug apremilast (APR) with saccharin.

Methods: Cocrystals of APR were prepared using a solvent evaporation technique. The saturated solubility study and in vitro dissolution study of cocrystals were carried out. The prepared cocrystals were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The topical gel of APR cocrystals was formulated optimized and evaluated using 3-level factorial design.

Results: The cocrystals of APR were prepared in 1:1 molar ratio with saccharin. APR cocrystals showed the improvement in solubility and dissolution as compared to pure APR. The formation of cocrystals was confirmed from a change in the endothermic peak of DSC and from shifting of FTIR spectra of cocrystals. Crystallinity of cocrystal was confirmed from XRD pattern and noteworthy change in 2θ values of the intense peak. The topical gel of APR cocrystals was formulated and optimized using 3-level factorial design using Carbapol-940 and hydroxypropyl methylcellulose as a gelling agent.

Conclusion: The cocrystals with altered physicochemical properties of APR was prepared with saccharin and formulated as a topical gel to overcome the problems related to oral administration.


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Alaoui YE, Sefrioui R, Bensouda Y, Rahali Y. Solublization of acetaminophen using phospholipid and nonionic surfactants optimized by experimental design. J Chem Pharm Res 2014;6:39-46.

Patel JN, Rathod MD, Patel NA, Modasiya MK. Technique to improve the solubility of poorly soluble drugs. Int J Pharm Life Sci 2012;3:1459-69.

Dhillon B, Goyal NK, Malviya R, Sharma PK. Poorly water soluble drug: Change in solubility for improved dissolution characteristics review. Golden J Pharmacol 2014;8:26-35.

Chaudhari S, Nikam S, Khatri N, Wakade S. Co-crystals: A review. J Drug Deliv Ther 2018;8:350-8.

Nate S, Ann N. Pharmaceutical co-crystals and their physicochemical properties. Cryst Growth Des 2009;9:2950-67.

Panzade P, Shendarkar G, Shaikh S, Rathi BP. Pharmaceutical co-crystals of piroxicam: Design, formulation and evaluation. Adv Pharm Bull 2017;7:399-408.

Rahman FA, Rahim SA, Tan CC, Low SH, Ramle NA. Carbamazepine-fumaric acid and carbamazepine-succinic acid co-crystal screening using solution based method. Int J Chem Eng Appl 2017;8:136-40.

Erizal Z, Yeyet CS, Halim A, Fitriani L, Sundani NS. Formulation and characterization of sulfamethoxazole-trimethoprim co-crystal by milling process. J Appl Pharm Sci 2017;7:169-73.

Md Halid K, Muqtader M, Essam E, Farhat F, Alalaiwe A, Muzaffar I. Preparation of sustained release aprimilast-loaded PLGA nanoparticles: In vitro characterization and in vivo pharmacokinetic study in rats. Int J Nanomed 2018;14:1587-95.

Pawar H, Sarasja S, Parkash C. A novel nano-gel formulation of methotrexate for topical treatment of psoriasis: Optimization, in vitro and in vivo evaluation. Pharm Dev Technol 2015;21:554-62.

Vangipuram R, Alikhan A. Aprimilast for the management of moderate to severe plaque psoriasis. Expert Rev Clin Pharmacol 2017;10:349-60.

Ganarajan G, Sharma DC, Tangri P, Kothiyal P. Design and characterization of aprimilast loaded emulgel for topical treatment. Int J Pharm Biol Sci 2018;8:552-62.

Sevukarajan M, Thanuja B, Sodanapalli R, Nair R. Synthesis and characterization of pharmaceutical co-crystal: Aceclofenac-nicotinamide. J Pharm Sci Res 2011;3:1288-93.

Payghan SA. Preparation and characterization of molecular complexes of finofibrate co-crystal. Asian J Pharm 2017;11:745-58.

Londhe V, Shah K, Borhade S. Utilization of co-crystalization for solubility enhancement of poorly soluble, antiretroviral drug-ritonavir. Int J Pharm Pharm Sci 2014;6:556-8.

Ranjan S, Devarapalli R, Kundu S, Vangala VR, Ghosh A, Reddy CM. Three new hydrochlorothiazide co-crystals: Structural analysis and solubility studies. J Mol Struct 2017;1133:405-10.

Panzade P, Shendarkar G. Design and preparation of zaltoprofen-nicotinamide pharmaceutical co-crystal via liquid assisted grinding method. Indian J Pharm Educ 2019;53:S563-70.

Sai Priyanka NV, Neeraja P, Mangilal T, Kumar MR. Formulation and evaluation of gel loaded with microspheres of aprimilast for transdermal delivery system. Asian J Pharm Clin Res 2019;12:411-7.

Sopyan I, Fudholi A, Muchtaridi M, Sari IP. Simvastatin-nicotinamide co-crystal: Design, preparation and preliminary characterization. Trop J Pharm Res 2017;16:297-303.

Sopyan I, Fudholi A, Muchtaridi M, Sari IP. Co-crystalization: A tool to enhance the solubility and dissolution rate of simvastatin. J Young Pharm 2017;9:183-6.

Pathak C, Savjani K, Gajjar A, Savjani J. Co-crystal formation of paracetamol with indomethacin and mefenamic acid: An efficient approach to enhance solubility. Int J Pharm Pharm Sci 2013;5:414-9.

Gupta A, Mishra AK, Singh AK, Gupta V, Bansal P. Formulation and evaluation of topical gel of diclofenac sodium using different polymers. Drug Invent Today 2010;2:250-3.

Khadka D, Gulzar MA, Kowti R, Dhakal P, Achary A. Formulation and evaluation of transdermal gel of lornoxicum and comparative diffusion study by iontophoresis and chemical enhancers. Int J Adv Pharm Res 2015;6:40-9.

Ramchandani U, Sangameswaran B. Formulation and evaluation of topical gel of kitoprofen using different polymers. Int J Pharm Biol Arch 2013;4:323-6.

Markar B, Devgan M, Chowdary YA, Ramaiah M. Formulation and evaluation of herbal gel containing extract of cedrus deodara. Int J Pharm Chem Sci 2015;4:67-9.

Bhuyian UH, Rashid H, Mohsin MD, Tahera KT. An overview: Stability study of pharmaceutical products and shelf life prediction. Eur J Biomed Pharm Sci 2015;2:30-40.

Pokharana M, Vaishnav R, Goyal A, Shrivastava A. Stability testing of guidelines of pharmaceutical products. J Drug Deliv Ther 2018;8:169175.

Gadade D, Rathi PB. Solubility enhancement of lornoxicam by crystal engineering. Indian J Pharm Sci 2017;79:277-86.

Gadade D, Pekamwar S, Mahendra DS. Crystal engineering of antiviral agent efavirenz for solubility enhancement. J Drug Deliv Ther 2018;8:86-91.



How to Cite

MANE, T., and M. MOHITE. “DESIGN, FORMULATION, AND CHARACTERIZATION OF APREMILAST – SACCHARIN COCRYSTALS LOADED WITH TOPICAL GEL”. Asian Journal of Pharmaceutical and Clinical Research, vol. 13, no. 7, July 2020, pp. 60-67, doi:10.22159/ajpcr.2020.v13i7.37693.



Original Article(s)