Development of polycomplex carriers based on hydroxypropyl cellulose and Carbopol® for gastroretentive drug delivery

Introduction. As a result of the study, the process of formation of interpolymer complex (IPC) between pairs of polymers was studied between hydroxypropyl cellulose (HPC) and different brands of Carbopol® 71G, 971, 974 at two mixing orders in 95 % ethanol at pH = 3,5 (acidified with 0,1 M HCl) by turbidimetry, IR-spectroscopy, thermogravimetric analysis (TGA). The performed experiments confirmed the formation of an interpolymer complex (IPC) between these pairs of polymers. According to the research results, the prospective ratio of a pair of HPC and Carbopol® 71G was selected in a stoichiometric equimolar ratio regardless of the mixing order. The compatibility of the studied polymers in the composition of the resulting polycomplex was confirmed, using the method of modulated differential scanning calorimetry (mDSC). The obtained IPC had a stoichiometric composition of Carbopol® 71G / HPC 2 : 1 (by moles), according to the elemental analysis. Swelling of matrices based on the synthesized IPC, as well as matrices from individual polymers and their physical mixture (PM), was carried out in a medium simulating stomach acid in comparison with the original polymers. The analysis of the of acyclovir release from the produced carriers was also carried out in a 0.1 M HCl media and showed the prospects of the developed system for creating a carrier with targeted release of drugs into a model environment simulating an empty stomach. The IPC samples showed low mucoadhesive properties compared to individual polymers and their physical mixture. The development of new carriers for drug delivery is one of the key areas of pharmaceutical technology. In this regard, special attention is paid to polymeric substances, carriers based on which provide a reduction in side effects, increased bioavailability and prolongation of the drug action. Gastroretentive delivery systems are of interest in the development of new dosage forms that allow regulating the rate of release of the active pharmaceutical ingredient (API) in the stomach.

Aim. Development of a polycomplex carrier based on hydroxypropyl cellulose with Carbopol® for gastroretentive delivery of acyclovir.

Materials and methods. The selection of IPC – formation conditions was carried out using the methods of turbidimetry, IR-spectroscopy, and TGA. The obtained optimal polycomplex carrier composition was characterized using modulated differential scanning calorimetry (mDSC) and IR-spectroscopy. The swelling of the matrices based on the synthesized polycomplex was studied in an environment that imitating stomach acid. The acyclovir release from the resulting matrices was studied in modeling media using method 1 (USP I) "basket method". Mucoadhesion was studied using a TA.XTplus texture analyzer (Stable Micro Systems, Surrey, UK) on mucin compacts.

Results and discussion. The formation of IPC occurs through the formation of hydrogen bonds between the —OH groups of macromolecular units of linear HPC and —COOH groups of rare-crosslinked polyacrylic acid (rPAA) in the composition of the used brands of Carbopol’s. The leftward shift of the characteristic band to 1730 cm^–1 in the FTIR spectra of the polycomplexes confirms the formation of IPCs. The IPCs are characterised by a single glass transition temperature (T_g = 91,0 ± 2,1 ºC). Elemental analysis revealed a two-fold molar excess of the rare cross-linked polymer (Carbopol® 71G) over the linear one (HPC). Throughout the entire experiment to study the kinetics of swelling, the compacted matrices retain their shape, increasing in size. Monitoring of possible structural transformations was carried out, using thermal analysis of samples of polycomplex matrices in the process of assessing their swelling, to confirm the stability of the polycomplex in an acidic environment. According to the results of the model API release kinetics, the maximum concentration of acyclovir released into the media is observed at 30 minutes of the experiment and equal 98.5 %. Whereas for HPC matrices, the maximum concentration is achieved after 2 hours, and for matrices based on Carbopol® 71G and their PM only in the final part of the experiment. The synthesized IPC was characterized by low mucoadhesion capacity on mucin compacts compared to individual polymers and the PM.

Conclusion. As a result of the study, optimal conditions for IPC – formation between pairs of polymers HPC and different brands of Carbopol® (71G, 971 and 974) were selected. Turbidimetry, IR-spectroscopy and TGA methods proved the formation of polycomplexes based on HPC and various brands of Carbopol®. The IPC HPC / Carbopol® 71G of stoichiometric composition, confirmed by elemental analysis, was characterized using thermal and spectral methods. The study of the release of acyclovir from the obtained matrices has shown the promise of using the developed systems for oral gastroretentive delivery.

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