Author(s): Nirmal Shah, Dhiral Patel, Dipti Gohil, Avinash Kumar Seth, Dhaivat Parikh


DOI: 10.52711/0974-360X.2024.00291   

Address: Nirmal Shah1*, Dhiral Patel1, Dipti Gohil1, Avinash Kumar Seth1, Dhaivat Parikh2
1Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Piparia - 391760, Vadodara, Gujarat, India.
2Department of Pharmaceutics, Institute of Pharmacy, Nirma University, S. G. Highway, Ahmedabad – 382481, Gujarat, India.
*Corresponding Author

Published In:   Volume - 17,      Issue - 4,     Year - 2024

Objectives: Cilnidipine has limited 25-30% of bioavailability due to BCS class II category drug. The aim of present work was to improve the solubility followed by dissolution rate of cilnidipine by formulation of nanosuspension. Materials and Methods: The nanosuspensionwas developed usingnanoprecipitation techniqueaidingultra-sonication with solvent (Dimethyl sulfoxide), antisolvent (water) and stabilizer (polyvinyl alcohol). The nano formulation was statistically optimized using Design Expert software by theBox-Behnken design. The concentration of Poly Vinyl Alcohol, Volume of Antisolvent and Stirring Time were considered as independent factors whereas Particle size and polydispersity index were considered as dependent factors. Results: The particle size of nanosuspension was found 178.57nm with narrow polydispersity index of 0.130. The microscopy study confirmed amorphous nature particles with rough surface. The zeta potential of 4.55 ±2.78 for optimized formulation finds stability of formulation during storage. The differential scanning calorimetry study and X-ray diffraction pattern showed the crystalline cilnidipine drug was converted to amorphous form upon precipitation into nanoparticles. Due to the nanonization of cilnidipine, the dissolution profile was noted as 92.41±3.56% which was significantly improved as compared with plain drug release data. The stability data showed satisfactory result for 2 months. Conclusion: It is summarized that the nanoprecipitation technique with ultra-sonication is approaching method for the formulation of homogenous nanosuspension with uniform sized dispersion of cilnidipine. Therefore, it can be assumed that the upon the enhancement in dissolution rate, the cilnidipine loaded nanosuspension may lead to improved absorption of drug from intestine followed by significant improvement in bioavailability.

Cite this article:
Nirmal Shah, Dhiral Patel, Dipti Gohil, Avinash Kumar Seth, Dhaivat Parikh. Enhancement in Dissolution Profile of Cilnidipine by Nanonization Technique: Optimization by Box-Behnken design. Research Journal of Pharmacy and Technology.2024; 17(4):1832-8. doi: 10.52711/0974-360X.2024.00291

Nirmal Shah, Dhiral Patel, Dipti Gohil, Avinash Kumar Seth, Dhaivat Parikh. Enhancement in Dissolution Profile of Cilnidipine by Nanonization Technique: Optimization by Box-Behnken design. Research Journal of Pharmacy and Technology.2024; 17(4):1832-8. doi: 10.52711/0974-360X.2024.00291   Available on:

1.    Patravale VB, Date AA, Kulkarni RM. Nanosuspensions: a promising drug delivery strategy. Journal of Pharmacy and Pharmacology. 2004; 56(7): 827-840.
2.    Chingunpituk J. Nanosuspension Technology for Drug Delivery. Walailak J Sci Technol. 2007; 4(2): 139-153.
3.    Jacobs C, Muller RH. Production and characterization of a budesonide nanosuspension for pulmonary administration. Pharmaceutical Research. 2002; 19(2): 189-194.
4.    Chandra KS, Ramesh G. The fourth-generation Calcium channel blocker: Cilnidipine. Indian Heart J. 2013; 65(6): 691-695.
5.    Takahara A. Cilnidipine: a new generation Ca2+ channel blocker with inhibitory action on sympathetic neurotransmitter release. Cardiovasc Ther. 2009; 27(2): 124-139.
6.    Yadav GV, Singh SR. Nanosuspension: A promising drug delivery system. Pharmacophore. 2012; 3(5): 217-243.
7.    Bohm BH, Muller RH. Lab-scale production unit design for nanosuspensions of sparingly soluble cytotoxic drugs. Pharm Sci Technol Today. 1999; 2(8): 336-339.
8.    Ain-Ai A, Gupta PK. Effect of arginine hydrochloride and hydroxypropyl cellulose as stabilizers on the physical stability of high drug loading nanosuspensions of a poorly soluble compound. Int J Pharm. 2008; 351(1-2): 282-288.
9.    Patel M, Shah A, Patel NM, et al. Nanosuspension: A novel approach for drug delivery system. Journal of Pharmaceutical Science and Bioscientific Research. 2011; 1(1): 1-10.
10.    Dressman JB, Amidon GL, Reppas C, et al. Dissolution testing as a prognostic tool for oral drug absorption: immediate release dosage forms. Pharmaceutical Research. 1998;15:11-22.
11.    Muller RH, Peters K. Nanosuspensions for the formulation of poorly soluble drugs: I. Preparation by a size-reduction technique. Int J Pharm. 1998; 160(2): 229-237.
12.    Sarika V. Khandbahale. A Review- Nanosuspension Technology in Drug Delivery System. Asian J. Pharm. Res. 2019; 9(2): 130-138
13.    Paun J.S., Tank H.M. Nanosuspension: An Emerging Trend for Bioavailability Enhancement of Poorly Soluble Drugs. Asian J. Pharm. Tech. 2012; 2(4): 157-168.
14.    Atul Phatak, Pallavi Jorwekar, P.D. Chaudhari. Nanosuspensions: A Promising Nanocarrier Drug Delivery System. Research J. Pharma. Dosage Forms and Tech. 2011; 3(5): 176-182 .
15.    Muller RH, Bohm BH, Grau J, et al. Nanosuspensions: a formulation approach for poorly soluble and poorly bioavailable drugs. In, Donald L. Wise, eds. Handbook of Pharmaceutical Controlled Release Technology (1st ed). CRC Press; Florida; 2000: 345-357.
16.    Rabinow BE. Nanosuspensions in Drug Delivery. Nat Rev Drug Discov. 2004; 3(9): 785-796.
17.    Lakshmi P, Kumar G. Nanosuspension Technology. Int J Pharm Pharm Sci. 2010; 2(4): 58-70.
18.    Kayser O. Nanosuspensions for the formulation of aphidicolin to improve drug targeting effects against Leishmania Infected Macrophages. Int J Pharm. 2000; 196(2): 253-256.
19.    Muller RH, Jacobs C. Buparvaquone mucoadhesive nanosuspension: preparation, optimisation and long-term stability. Int J Pharm. 2002; 237(1-2): 151-161.
20.    Shah NV, Seth AK, Balaraman R, et al. Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study. J Adv Res. 2016; 7(3): 423-434.
21.    Pandya KD, Shah NV, Gohil DY, et al. Development of Risedronate Sodium-loaded Nanosponges by Experimental Design: Optimization and in vitro Characterization. Indian J Pharm Sci. 2019; 81(2): 309-316.
22.    Gohil D, Shah N, Maheshwari RA. Effect of Formulation Variables on Fabrication of Risperidone Loaded Nanoparticles for Sustained Drug Delivery. Indian Journal of Pharmaceutical Education and Research. 2022; 56: 58-64.
23.    Sahu BP, Das MK. Nanosuspension for enhancement of oral bioavailability of felodipine. Appl Nanosci. 2014: 189-197.
24.    Sahu BP, Das MK. Nanoprecipitation with sonication for enhancement of oral bioavailability of furosemide. Acta Pol Pharm. 2014; 71(1): 129-137.
25.    Pawar Pravin, Yadav Adhikrao, Gharge Varsha. Different Techniques for Preparation of Nanosuspension with Reference to its Characterisation and various Applications - A Review. Asian J. Res. Pharm. Sci. 2018; 8(4): 210-216.
26.    Dode Raj H., Surawase Rajendra K.. Development and Evaluation of Nanosuspension of Albendazole by Nanoprecipitation. Research J. Pharma. Dosage Forms and Tech. 2022; 14(1): 1-6.
27.    Gadad AP, Tigadi SG, Dandagi PM, et al. Rosuvastatin loaded nanostructured lipid carrier: For enhancement of oral bioavailability. Indian Journal of Pharmaceutical Education and Research. 2016; 50(4): 605-611.
28.    Mou D, Chen H, Wan J, et al. Potent dried drug nanosuspensions for oral bioavailability enhancement of poorly soluble drugs with pH-dependent solubility. Int J Pharm. 2011; 413(1-2): 237-244.
29.    Shah N, Seth AK, Balaraman R. Bioavailability enhancement of poorly soluble raloxifene by designing inclusion complex with β–cyclodextrin. Int J Pharm Pharm Sci. 2015; 7(8): 205-211.
30.    Shah N, Gohil D and Patel S. Nanostructured Lipid Carriers (NLCs): A Modern Versatile Drug Delivery Vehicle. In Nanocarriers: Drug Delivery System: An Evidence Based Approach, Edited by Nirmal Shah. Springer Nature, Singapore. 2021; 1st ed:pp.107-124.
31.    Banavath H, Sivarama RK, Ansari T, et al. Nanosuspension: an attempt to enhance bioavailability of poorly soluble drugs. Int J Pharm Sci Res. 2010; 1(9): 1-11.
32.    Paun JS, Tank HM. Nanosuspension: An emerging trend for bioavailability enhancement of poorly soluble drugs. Asian Journal of Pharmacy and Technology. 2012; 2(4): 157-168.
33.    Muller RH, Bohm B (eds). Emulsions and nanosuspensions for the formulation of poorly soluble drugs. Florida;CRC Press. 1998: pp.141-147.
34.    Li W, Yang Y, Tian Y, et al. Preparation and in vitro/in vivo evaluation of revaprazan hydrochloride nanosuspension. Int J Pharm. 2011; 408(1-2): 157-162.
35.    Farooq SU, Kumar DS, Shahid AA. Formulation and Evaluation of Vitamin D3 (Cholecalciferol) Self-Nanoemulsifying Drug Delivery Systems for Enhancing Solubility. Int J Pharm Biol Sci. 2019; 9(3): 587-598.
36.    Shah N, Seth A, Balaraman R, et al. Oral bioavailability enhancement of raloxifene by developing microemulsion using D-optimal mixture design: optimization and in-vivo pharmacokinetic study. Drug Dev Ind Pharm. 2018; 44(4): 687-696.
37.    Lade S, Shah N, Burle S. Nanostructured lipid carriers: A vital drug carrier for migraine treatment. Res J Pharm Technol. 2022; 15(7): 3309-3316.
38.    Somasundaram I, Yadav BVN, Sathesh Kumar S. Formulation of PLGA Polymeric Nanosuspension containing Pramipexole Dihydrochloride for improved treatment of Parkinson’s Diseases. Res J Pharm Technol. 2016; 9(7): 810-816.
39.    Vidya Ashok Kheradkar, Jameel Ahmed S. Mulla. Nanosuspension: A Novel Technology for Drug Delivery. Asian J. Res. Pharm. Sci. 2023; 13(2): 106-0.
40.    M. K. Andhale, Jadhao. U. T., Rathod. D. A., Thoke S. T., Dhembre G. N. Formulation and Evaluation of Nanosuspension of Ambroxol Hyrochloride. Asian J. Pharm. Tech. 2023; 13(1): 4-8.
41.    Vijay Shinde, P Amsa, S Tamizharasi, D Karthikeyan, T Sivakumar, Aniket Kale. Formulation and Characterization of Eudragit RS 100 Nanosuspension for Ocular Delivery of Indomethacin. Research J. Pharm. and Tech. 2010; 3(3): 854-860.
42.    Mistry Khushboo, Kavya Naik, Vasanthi, Alicia Menezes, Anup Naha, K.B. Koteshwara, K. Girish Pai. Formulation and Evaluation of Irbesartan nanosuspension for Dissolution Enhancement. Research J. Pharm. and Tech. 2017; 10(9): 3043-3048.

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