The study on the development of self-emulsifying compositions with simvastatin

Authors

DOI:

https://doi.org/10.24959/nphj.23.104

Keywords:

self-emulsifying compositions; increased bioavailability; insoluble substances; simvastatin

Abstract

Self-emulsifying compositions are the basis of oral drug delivery systems used to improve the solubility and increase the bioavailability of active pharmaceutical ingredients that are poorly soluble in the aqueous medium of gastric juice.

Aim. To develop self-emulsifying compositions using simvastatin as an active pharmaceutical ingredient.

Materials and methods. During the development of the composition of the self-emulsifying mixture, excipients, such as solvents, co-solvents, surfactants and co-surfactants, allowed in pharmaceutical production were used. The studies of solubility, the formation rate of emulsions of the self-emulsifying composition and stability were carried out by generally accepted methods according to the methods of the SPhU and other valid normative documents.

Results and discussion. The studies of the solubility of simvastatin allowed choosing a mixture of castor oil and PEG-40 GRO as a solvent, which improved the solubility of the substance in oil. It was determined that it was efficient to use Tween-80 as the main surfactant. Glycerol monostearate, distilled monoglycerides, polyethylene oxide-400, polyethylene oxide-1500 and polyethylene glycol-100 stearate were introduced into the composition as co-surfactants. It was found that the compositions, which included polyethylene oxide-400 and polyethylene oxide-1500, had significantly worse indicators of the formation rate of emulsions than the rest of the samples. The sample containing distilled monoglycerides did not withstand a decrease in the pH value of the medium.

Conclusions. According to the results obtained, samples containing castor oil, PEG-40 hydrogenated castor oil, Tween-80, glycerol monostearate or PEG-100 stearate were selected for further research.

Author Biographies

L. A. Bodnar , National University of Pharmacy of the Ministry of Health of Ukraine

post-graduate student of the Department of Pharmaceutical Technology of Drugs

N. P. Polovko, National University of Pharmacy of the Ministry of Health of Ukraine

Doctor of Pharmacy (Dr. habil.), professor of the Department of Pharmaceutical Technology of Drugs

References

Kaushik D. Recent Developments in Self-microemulsifying Drug Delivery System: An Overview. Asian Journal of Pharmaceutics. 2019. Vol. 13, № 2. P. 59–72. DOI: https://doi.org/10.22377/ajp.v13i02.3101.

Formulation Studies of Solid Self-Emulsifying Drug Delivery System of Ivermectin / V. P. Patel et al. Folia Medica. 2018. Vol. 60, № 4. P. 580–592. DOI: 10.2478/folmed-2018-0024.

Formulation Development of an Albendazole Self-Emulsifying Drug Delivery System (SEDDS) with Enhanced Systemic Exposure / A. K. Meena et al. Acta Pharm. 2012. Vol. 62. P. 563–580. DOI: 10.2478/v10007-012-0031-0.

Gumaste S. G., Dalrymple D. M., Serajuddin Abu T. M. Development of Solid SEDDS, V: Compaction and Drug Release Properties of Tablets Prepared by Adsorbing Lipid-Based Formulations onto Neusilin® US2. Pharm Res. 2013. Vol. 30. P. 3186–3199. DOI: 10.1007/ s11095-013-1106-4.

Shukla J. B., Jani G. K., Omri A. W. Formulation and evaluation of Oral Self Microemulsifying Drug Delivery System Of Candesartan Cilexetil. International Journal of Pharmacy and Pharmaceutical Sciences. 2016. Vol. 8. P. 238–243.

Державна фармакопея України / ДП «Український науковий фармакопейний центр якості лікарських засобів». 2-ге вид. Т. 2. Харків : ДП «Український науковий фармакопейний центр якості лікарських засобів», 2014. 723 с.

European Pharmacopoeia. 8th ed. Strasbourg: European Department for the Quality of Medicines, 2013. 3655 p.

The Japanese Pharmacopoeia. 18th ed. The MHLW Ministerial Notification № 220. 2021. 2587 p.

Державна фармакопея України / ДП «Український науковий фармакопейний центр якості лікарських засобів». 2-ге вид. Т. 1. Харків : ДП «Український науковий фармакопейний центр якості лікарських засобів», 2015. 1126 с.

Yasser M., Gad Sh., El-Sayed M., Ghorab M. The Effect of Converting Liquid Valsartan SNEDDS Into Solid SNEDDS Using Different Solid Carriers on Its Performance. International Journal of Biological & Pharmaceutical Research. 2013. Vol. 4, № 12. P. 1015–1026. DOI: 10.13140/RG.2.2.34640.12808.

Bhattacharya S., Mishra Sh., Prajapati B. G. Design and Development of Docetaxel Solid Self-Microemulsifying Drug Delivery System Using Principal Component Analysis and D-Optimal Design. Asian Journal of Pharmaceutics. 2018. Vol. 12, № 1. P. 122–144. DOI: https://doi.org/10.22377/ajp.v12i01.2051.

Tamboli J. A., Mohite Sh. K. Development of Solid Self-Microemulsifying Drug Delivery System of Diacerein For Enhanced Dissolution Rate. Asian Journal of Pharmaceutical and Clinical Research. 2019. Vol. 12, Issue 2. P. 315–319. DOI: https://doi.org/10.22159/ ajpcr.2019.v12i2.29500.

Preparation and In Vitro/In Vivo Evaluation of Puerarin Solid Self-Microemulsifying Drug Delivery System by Spherical Crystallization Technique / G. Cheng et al. AAPS PharmSciTech. 2016. Vol. 17, № 6. DOI: 10.1208/s12249-015-0469-8.

Improved Oral Bioavailability Of Poorly Water-Soluble Indirubin By A Supersaturatable Self-Microemulsifying Drug Delivery System / Zh. Q. Chen et al. International Journal of Nanomedicine. 2012. Vol. 7. P. 1115–1125. DOI: 10.2147/IJN.S28761.

Pandey V., Kohli S. Peg-5 Oleate Based Self Microemulsifying Drug Delivery System: As a Versatile Approach in Oral Bioavailability Enhancement of Anti-Diabetic Agent: Formulation Design, vitro/In vivo Evaluation & Stability Studies. Global Journal of Pharmacy & Pharmaceutical Sciences. 2018. Vol. 5. Issue 5. DOI: 10.19080/GJPPS.2018.05.555671.

Development and Evaluation of Raloxifene-Hydrochloride-Loaded Supersaturatable SMEDDS Containing an Acidifier / J. H. Lee et al. Pharmaceutics. 2018. Vol 10. № 78. DOI: 10.3390/pharmaceutics10030078.

Strategic Approach to Developing a Selfmicroemulsifying Drug Delivery System to Enhance Antiplatelet Activity and Bioavailability of Ticagrelor / Y. G. Na et al. International Journal of Nanomedicine. 2019. Vol. 14. P. 1194–1212. DOI: 10.2147/IJN.S190426.

ГОСТ 29188.3-91 Изделия косметические. Методы определения стабильности эмульсии. Москва : Изд-во стандартов, 1992. 4 c.

Formulation, characterization and optimization of valsartan self-microemulsifying drug delivery system using statistical design of experiment / B. K. Poudel et al. Chem. Pharm. Bull. 2012. Vol. 60, № 11. P. 1409–1418. DOI: 10.1248/cpb.c12-00502.

Published

2023-02-17

Issue

Section

Technology of Medicines