FORMULATION AND PHARMACOKINETIC STUDY FOR LIQUISOLID COMPACTS OF CINACALCETHCl
DOI:
https://doi.org/10.22159/ijap.2025v17i1.52296Keywords:
Kawakita analysis, Heckle analysis, dissolution rate, and Pharmacokinetic studyAbstract
Objective: The objective of this study is to enhance the flowability, compressibility, and oral bioavailability of Cinacalcet Hydrochloride (HCl) using the liquisolid technique. It is a calcimimetic drug approved for treating secondary hyperparathyroidism in chronic kidney disease patients, faces challenges due to its poor aqueous solubility and low bioavailability (20-25 %).
Methods: To address this, we formulated cinacalcet HCl liquisolid compacts with tween 80 and labrasol as the non-volatile solvents, neusilin US2 as the carrier material, and aerosil as the coating material. Our comprehensive analysis included Fourier-transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Powder X-ray diffraction (P-XRD), kawakita analysis and heckel analysis, quality control tests and pharmacokinetic study.
Results: The liquisolid powders of cinacalcet HCl exhibited desirable flowability and compressibility for processing into a tablet dosage form. Kawakita and Heckel analysis revealed reduced cohesiveness and increased plasticity. FT-IR and DSC studies did not exhibit any interaction between drug and carriers. P-XRD study for liquisolid formulation did not exhibit any peaks due to the presence of cinacalcet HCl in molecular form.In-Vitro dissolution study revealed 37 times improvement in dissolution at 30 min. The Area Under the Curve (AUC)values showeda 2.5-fold increase in oral bioavailability.
Conclusion: Overall, the liquisolid approach promises to develop a stable and scalable solid dosage form with improved flowability, compressibility, and oral bioavailability
Downloads
References
Hermans, A., et al., Challenges and strategies for solubility measurements and dissolution method development for amorphous solid dispersion formulations. The AAPS Journal, 2022. 25(1): p. 11.
Savjani, K.T., A.K. Gajjar, and J.K. Savjani, Drug solubility: importance and enhancement techniques. International Scholarly Research Notices, 2012. 2012.
Sruti, J., et al., Improvement in the dissolution rate and tableting properties of cefuroxime axetil by melt-granulated dispersion and surface adsorption. Acta pharmaceutica sinica B, 2013. 3(2): p. 113-122.
Agustina, R. and D. Setyaningsih, Solid Dispersion As A Potential Approach To Improve Dissolution And Bioavailability Of Curcumin From Turmeric (Curcuma Longa L.). Int J App Pharm [Internet], 2023: p. 37-4.
Paczkowska, M., et al., β-Cyclodextrin complexation as an effective drug delivery system for meropenem. European Journal of Pharmaceutics and Biopharmaceutics, 2016. 99: p. 24-34.
SOGALI, B.S. and R.M. KV, Comparative studies with different cyclodextrin derivatives in improving the solubility and dissolution of saquinavir. drugs, 2018. 8: p. 12.
Wang, B., et al., Enhancing bioavailability of natural extracts for nutritional applications through dry powder inhalers (DPI) spray drying: technological advancements and future directions. Frontiers in Nutrition, 2023. 10: p. 1190912.
Taldaev, A., et al., Modification of the Physicochemical Properties of Active Pharmaceutical Ingredients via Lyophilization. Pharmaceutics, 2023. 15(11): p. 2607.
Rasenack, N. and B.W. Müller, Dissolution rate enhancement by in situ micronization of poorly water-soluble drugs. Pharmaceutical research, 2002. 19: p. 1894-1900.
Shi, N., et al., Study on the properties of felodipine solid dispersions prepared by different technologies. Beijing da xue xue bao. Yi xue ban= Journal of Peking University. Health Sciences, 2016. 48(6): p. 1067-1073.
Spireas, S., Liquisolid systems and methods of preparing same. 2002, Google Patents.
Lu, M., et al., Liquisolid technique and its applications in pharmaceutics. Asian journal of pharmaceutical sciences, 2017. 12(2): p. 115-123.
Kanojiya, P.S., P.N. Ghodake, and R.N. Wadetwar, Design and optimization of liquisolid compact based vaginal sustained release tablet of antifungal agent for vaginal candidiasis. Journal of Dispersion Science and Technology, 2024. 45(3): p. 513-528.
Panda, S., et al., Liquisolid technique: a novel approach for dosage form design. Int J Appl Pharm, 2017. 9(3).
Franceschini, N., M.S. Joy, and A. Kshirsagar, Cinacalcet HCl: a calcimimetic agent for the management of primary and secondary hyperparathyroidism. Expert opinion on investigational drugs, 2003. 12(8): p. 1413-1421.
Padhi, D. and R. Harris, Clinical pharmacokinetic and pharmacodynamic profile of cinacalcet hydrochloride. Clinical pharmacokinetics, 2009. 48: p. 303-311.
Aleksić, I., et al., Liquisolid systems: Evaluation of the influence of formulation variables on the optimum liquid load. Archives of Pharmacy, 2022. 72(Notebook 1): p. 61-76.
Sinko, P.J., Martin's physical pharmacy and pharmaceutical sciences. 2023: Lippincott Williams & Wilkins.
Patra, C.N., et al., Design and characterization of aceclofenac and paracetamol spherical crystals and their tableting properties. Powder Technology, 2015. 274: p. 446-454.
Patra, C.N., et al., Applicability and comparative evaluation of wet granulation and direct compression technology to Rauwolfia serpentina root powder: a technical note. AAPS PharmSciTech, 2008. 9: p. 100-104.
Lachman, L., H.A. Lieberman, and J.L. Kanig, The theory and practice of industrial pharmacy. 1976: Lea & Febiger Philadelphia.
Bruschi, M.L., Strategies to modify the drug release from pharmaceutical systems. 2015: Woodhead Publishing.
Haleem, R.M., et al., Quality in the pharmaceutical industry–A literature review. Saudi pharmaceutical journal, 2015. 23(5): p. 463-469.
Routray, S.B., et al., Analytical Quality by Design Based Systematic Development and Optimization of a Sensitive Bioanalytical Method for Estimation Cinacalcet HCl in Rabbit Serum. Journal of Pharmacy and Bioallied Sciences, 2021. 13(4): p. 360-366.
Nakaweh, A., et al., Deep Eutectic System-Based Liquisolid Nanoparticles as Drug Delivery System of Curcumin for In-Vitro Colon Cancer Cells. Journal of Pharmaceutical Innovation, 2024. 19(2): p. 1-11.
Panigrahi, K.C., C.N. Patra, and M.B. Rao, Quality by design enabled development of oral self-nanoemulsifying drug delivery system of a novel calcimimetic cinacalcet HCl using a porous carrier: in vitro and in vivo characterisation. AAPS PharmSciTech, 2019. 20: p. 1-17.
Williams, H.D., et al., Lipid-based formulations solidified via adsorption onto the mesoporous carrier Neusilin® US2: Effect of drug type and formulation composition on in vitro pharmaceutical performance. Journal of pharmaceutical sciences, 2014. 103(6): p. 1734-1746.
Gumaste, S.G., D.M. Dalrymple, and A.T. Serajuddin, Development of solid SEDDS, V: compaction and drug release properties of tablets prepared by adsorbing lipid-based formulations onto Neusilin® US2. Pharmaceutical research, 2013. 30: p. 3186-3199.
Komínová, P., L. Kulaviak, and P. Zámostný, Stress-Dependent Particle Interactions of Magnesium Aluminometasilicates as Their Performance Factor in Powder Flow and Compaction Applications. Materials, 2021. 14(4): p. 900.
Rao, K.S., M. Nagabhushanam, and K. Chowdary, In vitro dissolution studies on solid dispersions of mefenamic acid. Indian Journal of Pharmaceutical Sciences, 2011. 73(2): p. 243.
Komala, D.R., et al., Competence of raloxifene hydrochloride loaded liquisolid compacts for improved dissolution and intestinal permeation. Journal of Drug Delivery Science and Technology, 2015. 30: p. 232-241.
Bhatia, M., et al., Formulation and optimization: Liquisolid of domperidone for solubility enhancement. ACTA Pharmaceutica Sciencia. 62(3).
Dindigala, A.K., C.S. Reddy, and A. Makineni, Enhancement of Solubility and Dissolution Rate of Simvastatin Tablets by Liquisolid Compact Approach. Journal of Drug Delivery and Therapeutics, 2024. 14(8): p. 64-72.
Patra, C.N., et al., QbD Enabled Formulation Development of Nanoemulsion of Nimodipine for Improved Biopharmaceutical Performance. Journal of Pharmaceutical Innovation, 2023: p. 1-19.
Published
How to Cite
Issue
Section
Copyright (c) 2024 Somesu Macha, Dr. Ch Niranjan Patra, Dr. Goutam Kumar Jena, Dipthi Shree, Dr. Sudarsan Biswal
This work is licensed under a Creative Commons Attribution 4.0 International License.
