THE MAIN APPROACHES TO FORMULATION OF PARENTERAL SUSPENSION BASED ON HYDROCORTISONE ACETATE DRUG SUBSTANCE IN COMBINATION WITH LOCAL ANESTHETICS OF LIDOCAINE HYDROCHLORIDE
DOI:
https://doi.org/10.11603/2312-0967.2017.3.8113Keywords:
parenteral suspension, hydrocortisone acetate, lidocaine hydrochloride, excipients, formulation, quality target product profile, critical quality attributes, ICH Q8.Abstract
The aim of the work. Scientifically justifying the optimal amounts choice of excipients in the formulation of the parenteral suspension based on hydrocortisone acetate drug substance in combination with local anesthetic of lidocaine hydrochloride, taking into account the requirements of ICH Q8 «Pharmaceutical development» guideline.
Materials and Methods. The approaches described in the ICH Q8 «Pharmaceutical development» were used and the following analytical methods were used: high performance liquid chromatography (SPU 2.2.29), potentiometric titration (SPU 2.2.20), laser diffraction (SPU 2.9.31), potentiometric determination of pH (SPU 2.2.3), viscosity (SPU 2.2.8), microbiological tests (SPU 2.6.1, 2.6.14).
Results and Discussion. The quality target product profile of the parenteral suspension «Hydrocortisone acetate + lidocaine hydrochloride» was developed and an assessment was made for the determination of critical quality attributes within conducted researches according to ICH Q8 «Pharmaceutical development» guideline. All identified formulation risks were justified, and those that had a «medium» and «high» levels according to the assessment, by ways of the variability of variables in the experimental studies was reduced to «low» level.
The approach to choosing of the concentrations of buffer system components have been demonstrated and the experimentally confirmed the optimality range of the pH values of suspension at the range of 5.0 – 7.0 for the stability of the finished dosage form.
After conducting the entire spectrum of research, a reassessment of risks was carried out, which confirmed the reduction of the above risks to acceptable by ways of full compliance with the main quality attributes of the finished dosage form.
Conclusions. Based on conducted research, the choice of optimal amounts of excipients within the formulation of parenteral suspension based on hydrocortisone acetate drug substance in combination with local anesthetic of lidocaine hydrochloride, taking into account the requirements of ICH Q8 «Pharmaceutical development» guideline, was scientifically justified.References
Ukrainian Scientific Pharmacopoeial Center for Quality of Medicines. State Pharmacopoeia of Ukraine. [Державна Фармакопея України]. 2nd ed. Vol. 1. Kharkiv: Ukrainian Scientific Pharmacopoeial Center for Quality of Medicines; 2015, 1090-3. Ukrainian.
Kulshreshtha Alok K, Singh Onkar N, Wall G Michael, editors. Pharmaceutical suspensions From formulation development to manufacturing. London: Michael Springer New York Dordrecht Heidelberg; 2010.
Kachaput ОІ, Hureieva SМ. [The research of excipient`s assortment used in finished drug products in suspensions forms for injection, which are registered in Ukraine]. Farmatsevt chasop. 2015;2:36-9. Ukrainian.
International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. – Available from: http://www.ich.org/home.html.
International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH Q8. – Available from: http://www.ich.org/products/guidelines/quality/article/quality-guidelines.html
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