IMPROVEMENT OF SIMVASTATIN DISSOLUTION RATE USING DERIVATIVE NON-COVALENT APPROACH BY SOLVENT DROP GRINDING METHOD
DOI:
https://doi.org/10.22159/ijap.2020v12i1.35865Keywords:
Simvastatin, Non-covalent derivative, Solvent drop grinding, DissolutionAbstract
Objective: This study aimed to enhance the solubility of simvastatin using noncovalent derivatives (NCDs) with oxalic acid (OA), fumaric acid (AF), and nicotinamide (NK) as conformers.
Methods: NCDs were prepared using by a solvent drop grinding (SDG). The NCDs formed were evaluated for saturated solubility test, NCDs with the highest saturation solubility were then characterized by Fourier transform infrared spectrophotometry (FT-IR), differential scanning calorimeter (DSC), powder x-ray diffractometry (PXRD) and the particulate dissolution using type II of USP test.
Results: SV-OA NCDs showed the highest solubility; thus NCDS of SV-OA were characterized by X-ray diffraction showing a new peak at 2ϴ = 28.96 °C and differential scanning calorimeter showed a change of endothermic peak from 134.3 °C to 69 °C. Infrared spectroscopy indicated that there were no functional group changes from simvastatin, while the dissolution rate increased from 68.22% to 76.08%.
Conclusion: SV-OA NCDs show an increased profile of solubility and dissolution compared to pure simvastatin.
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References
Racz I. Drug formulation. John Wiley and Sons; 1989.
Shargel L, Yu ABC. Applied biopharmaceutics and pharmaco-kinetics. 4th Edit. Norwalk CT Appleton Lange; 1999. p. 573–605.
Zheng X, Hu SJ. Effects of simvastatin on cardiohemodynamic responses to ischemia-reperfusion in isolated rat hearts. Heart Vessels 2006;21:116–23.
Martin A, Swarbrick J, Cammarata A. Physical pharmacy. Philadelphia: LeaandFebiger; 1990. p. 559–637.
Mirza S, Miroshnyk I, Heinamaki J, Yliruusi J. Co-crystals: an emerging approach for enhancing properties of pharmaceutical solids. Dosis 2008;24:90–6.
Sopyan I, Fudholi A, Muchtaridi M, Puspitasari I. A simple effort to enhance solubility and dissolution of simvastatin using cocrystalization. Int J Pharm Pharm Sci 2016;8:342–6.
Trask AV, Jones W. Crystal engineering of organic cocrystals by the solid-state grinding approach. In: Organic solid-state reactions. Springer; 2005. p. 41–70.
Zaini E, Halim A, Soewandhi SN, Setyawan D. [Peningkatan laju pelarutan trimetoprim melalui metode kokristalisasi dengan nikotinamida]. J Farm Indones 2011;5:205–12.
Putra OD, Nugrahani I, Ibrahim S, Uekusa H. Pembentukan padatan semi kristalin dan ko-kristal parasetamol. J Mat Sains 2012;17:1–6.
Sekhon BS. Pharmaceutical co-crystals-a review. Ars Pharm 2009;5:99–100.
Sopyan I, Fudhloli A, Muchtaridi M, Sari IP, Permatasari D. A novel of derivative spectrophotometry as rapid and accurate method in application of simvastatin co-crystal assay. Int J Res Pharm Sci 2017;20:301–6.
Bag PP, Patni M, Reddy CM. A kinetically controlled crystallization process for identifying new co-crystal forms: fast evaporation of solvent from solutions to dryness. Cryst Eng Comm 2011;13:5650–2.
Harmita H. Buku ajar analisis fisikokimia]. Jakarta: Departemen Farmasi FMIPA UI; 2006.
Brittain HG. Theory and principles of polymorphic systems. In: Polymorphism in Pharmaceutical Solids. Informa Healthcare USA: New York; 2009.
Nugrahani I. Identifikasi interaksi padatan bahan aktif dan pengaruh interaksi amoksisilina trihidrat–kalium klavulanat terhadap potensi dan profil farmakokinetika]. Institut Teknologi Bandung; 2009.
Sopyan I, Sari IM, K IS. Solid state characterization of a novel physical interaction (paracetamil-chlorfeniramine maleate). Int J Appl Pharm 2018;6:21–5.
Sopyan I. Co-crystallization: a tool to enhance solubility and dissolution rate of simvastatin. J Young Pharm 2017;9:183–6.
Sopyan I, Fudholi A, Muchtaridi M, Sari IP. Simvastatin-nicotinamide co-crystal: design, preparation and preliminary characterization. Trop J Pharm Res 2017;16:297.