Development of the Technology for Producing Capsules with a Compound Extract of Oplopanax elatus, Sophora japonica, and Origanum vulgare Using a Risk-Based Approach

INTRODUCTION. The application of a risk-based approach to the development of a technology for producing hard gelatin capsules (HGC) with a compound extract allows the determination of critical process parameters and critical quality attributes, which forms the basis for creating quality management tools in the manufacture of the finished dosage form (FDF) and is consistent with the modern quality-by-design concept.

AIM. Development of a technology for producing hard gelatin capsules with a compound extract of Oplopanax elatus, Sophora japonica, and Origanum vulgare using a risk-based approach to the quality of the finished dosage form.

MATERIALS AND METHODS. The compound extract was obtained by concentrating a hydroalcoholic extract from a mixture of medicinal plant raw materials: roots and rhizomes of Oplopanax elatus, flower buds of Sophora japonica, and herb of Origanum vulgare. The granulate composition was developed using design of experiments. The granulate was filled into hard gelatin capsules. Standardization of the capsules was performed according to the Pharmacopoeia of the Eurasian Economic Union (EAEU) methods. Quantitative analysis of flavonoids was carried out by spectrophotometry, and qualitative analysis by thin-layer chromatography (TLC). Risk identification for capsule quality was performed using Ishikawa (fishbone) diagrams.

RESULTS. A laboratory-scale technology for the thick extract of Oplopanax, Sophora, and Origanum is proposed, based on four-fold ultrasonic remaceration with 70% ethanol, dividing the extractant into portions. This method yields an extract with an average flavonoid content of 2.63±0.16%. The composition and technology of the granulate with the compound extract were developed using wet granulation with readily available excipients. The obtained granulate had an average flavonoid content of 1.85±0.04%. A laboratory technology for HGC with an average flavonoid content of 1.56±0.04% is proposed. Critical quality attributes and critical process parameters for the FDF production were identified. The thick compound extract, granulate, and hard gelatin capsules obtained by the developed technology meet the design and pharmacopeial requirements for the quality attributes tested.

CONCLUSIONS. A technology for producing HGC with a compound extract of Oplopanax, Sophora, and Origanum has been developed, taking into account risk identification for FDF quality. The proposed technology is limited to the preliminary laboratory level of evaluating the parameters for HGC production. The results obtained allow further refinement of technological parameters, preparation of pilot batches, and assessment of quality risks within the framework of pharmaceutical development of the FDF.

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