Study of the Pharmaceutical Grade Polymers effect on the Dissolution of Practically Insoluble Antiretroviral Substances

Introduction. Many of new active pharmaceutical ingredients (APIs) have low solubility that can affect bioavailability negatively and therefore therapeutically efficacy as well. These APIs include the following antiretroviral substances: ritonavir, efavirenz, etravirine. There are various approaches to increase the dissolution of the APIs, for example, the preparation of solid dispersion systems (SDS), in which polymer is used as a drug carrier, and the other one is usage of surfactants. However, the techniques used to obtain SDS have a number of disadvantages: high temperatures, organic solvents and expensive equipment. In turn, surfactants affect the work of internal organs, have an irritating effect. Instead of these methods, they use pharmaceutical acceptable polymers, which are safer in comparison with low-molecular-weight surfactants and still act as surface-active agents.

Aim. Study of the pharmaceutical grade polymers effect on the dissolution of practically insoluble antiretroviral substances: ritonavir, efavirenz, etravirine.

Materials and methods. APIs: efavirenz form І (LLC "AMEDART", Russia, batch 010520); efavirenz reference standard (USP No. R09740); ritonavir form I (LLC "AMEDART", Russia, batch 010320); ritonavir form II (LLC "AMEDART", Russia, batch 010320); ritonavir reference standard
(USP No. H0M427); etravirine form І (LLC “AMEDART”, Russia, batch 010720); etravirine reference standard (MSN, India, batch ETV/A312/6/01). The dissolution of substances in polymer solutions was studied using the Paddle apparatus under the conditions recommended by the FDA for the drugs.

Results and discussion. The nature of the effect, which is, as defined, influenced by the type of polymer, the concentration of the polymer solution and the pH of the medium, is ambivalent. Both a substance dissolution increase and a decrease are possible. Polymers, such as hydroxypropylcellulose, hydroxypropylmethylcellulose, Eudragit® E PO, can significantly increase the dissolution of substances, while polyvinylpyrrolidone can block it in certain cases. The greatest increase in dissolution of ritonavir, efavirenz and etravirine was found in Eudragit®
E PO solutions.

Conclusion. The results of the study showed the feasibility of determining the bioavailability of dosage forms of practically insoluble APIs with the inclusion of polymer excipients in their formulations.

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