Development of Lyophilisates Based on Polymer-drug and Interpolyelectrolyte Complexes: Pharmacokinetic Assessment
Authors: Timergalieva V. R. , Sitenkov A. Yu. , Sitenkova (Bukhovets) A. V. , Elizarova E. S. , Gordeeva D. S. , Semina I. I. , Moustafine R. I. 
Published: November 2023

Introduction. Orally dispersible dosage forms are one of the new trends in the field of drug delivery systems. One type of such dosage forms is oral lyophilisates that are obtained by freeze-drying a pre-prepared mixture containing the active pharmaceutical ingredient (API) and excipients. This dosage form provides immediate release of the active pharmaceutical ingredient in the oral cavity using a less amount of excipients.

Aim. Pharmacokinetic studies of previously obtained lyophilisates based on the polymer-drug complex Eudragit® E PO / ibuprofen (PDC EPO-IB) and the interpolyelectrolyte complex (IPEC) Carbopol® Ultrez 10 / Eudragit® E PO (IPEC C10/EPO) and metronidazole.

Materials and methods. Lyophilisates of the following compositions were obtained: 1) 100 mg of metronidazole and 50 mg of IPEC C10/EPO or 2) 100 mg of PDC EPO-IB, the first or second composition of the carrier with API was dispersed in 50 % maltodextrin syrup, Span®80 was added – 1.42 % from the total mass of the mixture. The mixture was poured into blisters for tablets, frozen in a FreeZone 1L laboratory dryer (Labconco, USA) for 24 hours at a temperature of –49 °C, and the main drying was carried out at a pressure of 0.350 mbar. Soviet Chinchilla rabbits were administered one lyophilisate containing PDC EPO/IB or IPEC C10/EPO with metronidazole; the substances ibuprofen (50 mg) and metronidazole (100 mg) were used as reference drugs. The concentration of API was determined by high-performance liquid chromatography (HPLC) on an LC-20 Prominence chromatograph (Shimadzu Corporation, Japan) with UV detection. Pharmacokinetic parameters were calculated using a model-independent method using the Thermo KinetikaTM (version 5.0, Build 5.00.11, Thermo Fisher Scientific, USA) program.

Results and discussion. According to the obtained pharmacokinetic profiles, the maximum concentration of ibuprofen from EPO/IB PDC is achieved within the first hour after oral administration. The second peak in the profiles shows the absorption of the remaining portion of the API into the blood from the gastrointestinal tract (GIT), both in the case of EPO/IB PDC and in the case of ibuprofen from the substance. The relative bioavailability of EPO/IB PDC was Frel = 86.06 %. Lyophilisates based on IPEC C10/EPO provide the maximum concentration of metronidazole after 30 minutes (Cmax = 4.659 μg/ml). Relative bioavailability was Frel = 107.6 %.

Conclusion. According to studies, the maximum concentration of ibuprofen and metronidazole is achieved within the first hour after oral administration of lyophilisates containing PDC EPO-IB and IPEC C10/EPO. Absorption of medicinal substances in the oral cavity occurs due to the components included in the dispersible dosage form, as well as due to the presence of a ЕРО copolymer, PDC and an IPEC, which are able to linger on the oral mucosa due to the presence of mucoadhesive properties. Thus, the pharmacokinetic studies of ibuprofen and metronidazole from the obtained lyophilisates prove the suitability of the obtained forms for immediate release systems.