Improvement of solubility and dissolution rate of Biopharmaceutical Class II drug atorvastatin calcium by using an essential amino acid L-leucine

Hewa  Abdullah Hamadameen; Hemn Latef Qader; Anjam  Hama Abdullah

doi:10.15218/zjms.2022.008

Authors

Hewa Abdullah Hamadameen Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Hemn Latef Qader Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
Anjam Hama Abdullah Department of Pharmaceutics, College of Pharmacy, Hawler Medical University, Erbil, Iraq.

DOI:

https://doi.org/10.15218/zjms.2022.008

Keywords:

Atorvastatin calcium (ATC), Leucine (LUC), Solid dispersion (SD)

Abstract

Background and objective: Atorvastatin calcium is an antihyperlipidemic agent that is characterized by low aqueous solubility and high membrane permeability. This study was designed to enhance the solubility and the dissolution rate of atorvastatin calcium in the water and physiological pH (pH 6.8) by using L-Leucine as solubilizing agent utilizing different solid dispersion methods.

Methods: Solid dispersion masses were prepared by kneading method and solvent evaporation methods at different weight ratios (1:1, 1:2: and 1:4) of the drug to the carrier. Saturated solubility studies were carried out in aqueous media, and the in-vitro studies were performed in physiological pH Fourier transform infrared spectroscopy were used to detect any interaction between the drug and the carrier.

Results: The kneading method increase the solubility of atorvastatin calcium by 1.27, 1.43, and 1.81 folds from kneading method 1, kneading method 2, and kneading method 3, respectively. The solubility of atorvastatin calcium in solvent evaporation 1, solvent evaporation 2, and solvent evaporation 4 was increased by 2.53, 2.66, and 3.1 folds (P = 0.002). Solvent evaporation 2 (1:2 ratio) was selected as the best formula in terms of dissolution profile because it has faster and complete drug release after 5 minutes when compared with solvent evaporation 1, kneading method 1, kneading method 2, and kneading method 3 and contain less amount of L-Leucine when compared with solvent evaporation 3. Fourier transform infrared studies indicated no chemical reaction between the drug and carrier.

Conclusion: L-leucine significantly improved the solubility and dissolution profile of poorly water-soluble atorvastatin calcium.

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References

Shukla A, Bishnoi R, Dev S, Kumar M, Fenin V. Biopharmaceutical Classification System: Tool based prediction for drug dosage formulation. Adv Pharm J. 2017;2(6):204–9.

Nidhi K, Indrajeet S, Khushboo M, Gauri K, Sen D. Hydrotropy: A promising tool for solubility enhancement: a review. Int J Drug Dev & Res. 2011;3(2):26–33.

Rodde M, Divase G, Devkar T, Tekade A. Solubility and bioavailability enhancement of poorly aqueous soluble atorvastatin: In vitro, ex vivo, and in vivo studies. Bio Med Res Int. 2014;463895. https://doi.org/10.1155/2014/463895.

Jagtap S, Magdum C, Jadge D, Jagtap R. Solubility enhancement technique: A review. J Pharm Sci & Res. 2018;10(9):2205–11.

Kumar S, Singh P. Various techniques for solubility enhancement: An overview. J PharmInnov. 2016;5(1):23–8.

Raj A, Kumar Y. Preparation and evaluation of solid dispersion of nebivolol using solvent evaporation method. Int J Pharm Sci Drug Res. 2018; 10(4):322–8.

Karagianni A, Kachrimanis K, Nikolakakis I. Co-amorphous solid dispersions for solubility and absorption improvement of drugs: Composition, preparation, characterization and formulations for oral delivery. Pharmaceutics. 2018;10(3):98. https://doi.org/10.3390/pharmaceutics10030098.

Kannao Sh, Bakade B. Solid dispersion – a technique for solubility enhancement of weakly water-soluble drug-a review. Indo Am J Pharm. 2014;4(06):2839–48.

Ghosh P, Sharma H, Boruah N. Different methods used in solid dispersion. IOSR J Pharm. 2018;8(7):28–38.

Dey S, Chattopadhyay S, Mazumder B. Formulation and evaluation of fixed-dose combination of bilayer gastroretentive matrix tablet containing atorvastatin as fast-release and atenolol as sustained-release. Bio Med Res Int. 2014;2014:396106. https://doi.org/10.1155/2014/396106.

Wicaksono Y, Wisudyaningsih B, Siswoyo T. Enhancement of solubility and dissolution rate of atorvastatin calcium by co-crystallization. Trop J Pharm Res. 2017;16(7).

Shamsuddin, Fazil M, Ansari S, Ali J. Atorvastatin solid dispersion for bioavailability enhancement. J Adv Pharm Technol Res. 2016;7(1):22–6.

Mangal S, Nie H, Xu R, Guo R, Cavallaro R, Zemlyanove D, et al. Physico-chemical properties, aerosolization, and dissolution of co-spray dried azithromycin particles with L-Leucine for inhalation. Pharm Res. 2018;35(2):28.

Mayur T. Solubility enhancement of atorvastatin calcium by using microwave assisted solid dispersion preparation method. IJPRAS. 2015;4(1):51–6.

Sawant D, Ige P. Development and validation of simple UV-spectrophotometric method for estimation diclofenac sodium in bulk and tablet dosage form. Inventi. 2016;4:1–4.

Digambar M, Santosh J, Pandurang M, Ashpak T. Development and validation of UV spectrophotometric estimation of diclofenac sodium bulk and tablet dosage form using area under curve method. Pharma Tutor. 2015;3(4); 21–5.

Al Masum MD, Sharmin F, Islam S, Reza MD. Enhancement of solubility and dissolution characteristics of ibuprofen by solid dispersion technique. Dhaka Univ J Pharm Sci. 2012;11(1):1–6.

Hasnain M, Nayak A. Solubility and dissolution enhancement of ibuprofen by solid dispersion technique using peg 6000-pvp k 30 combination carrier. BJSEP. 2012; 21(1):118–32.

Sankari T, Al-Hariri S. Preparation and characterization of cefuroxime axetil solid dispersions using poloxamer 188. Braz J Pharm Sci. 2018;54(4):e17644. https://doi.org/10.1590/s2175-97902018000417644.

Hajare A, Jadhav P. Improvement of solubility and dissolution rate of indomethacin by solid dispersion in polyvinyl pyrrolidone K30 and poloxomer 188. Asian J Pharm Tech. 2012;2(3):116–22.

Kavitha K, Nachiya RAM. Formulation and evaluation of furosemide tablets as gastroretentive dosage forms using various polymers. IJSR. 2018;8(4):11–6.

Lakshmi V, Kalyan B, Kishore K, Raj M, Srinivasa P, Venkateswara B. Enhanced dissolution rate of atorvastatin calcium using solid dispersion with PEG 6000 by dropping method. J Pharm Sci & Res. 2010;2(8):484–91.

Varshosaz J, Khajavinia A, Ghasemlu M, Ataei E, Golshiri K, Khayam I. Enhancement in dissolution rate of piroxicam by two micronization techniques. Dissolution Technol. 2013;20(3):15–23. https://doi.org/10.14227/DT200313P15.

Bobe K, Subrahmanya C, Suresh S, Gaikwad D, Patil M, Khade T, et al. Formulation and evaluation of solid dispersion of Atorvastatin with various carriers. IJCP. 2011;2(1):1–6.

Varalakshmi T, Ramesh Ch, Jyothi I, Jyothi Y, Bharathi G, Babu P. Formulation and evaluation of solid dispersions of valsartan for dissolution rate enhancement. JPR. 2015;9(2):139–44.

Nidhi K, Indrajeet S, Khushboo M, Gauri K, Sen D. Hydrotropy: a promising tool for solubility enhancement: a review. Int J Drug Dev & Res. 2011;3(2):26–33.

Jadhav Y, Parashar B, Ostwaland P, Jain M. Solid dispersion: solubility enhancement for poorly water-soluble drug. Research J Pharm and Tech. 2012;5(2):190–7.

The United States pharmacopeia. Vol. 30. Rockville (MD): United States Pharmacopeial Convention; 2016. Uniformity dosage forms.

Wicaksono Y, Wisudyaningsih B, Siswoy T. Enhancement of solubility and dissolution rate of atorvastatin calcium by co-crystallization. Trop J Pharm Res. 2017;16(7):1497–502. http://doi.org/10.4314/tjpr.v16i7.6.

Kaur J, Aggarwal G, Singh G, Rana A. Improvement of drug solubility using solid dispersion. Int J Pharm Pharm Sci. 2012;4(2):47–53.