A long-lasting oral preformulation of the angiotensin II AT1 receptor antagonist losartan

Abstract

Losartan (Los), a non-peptidic orally active agent, reduces arterial pressure through specific and selective blockade of angiotensin II receptor AT1. However, this widely used AT1 antagonist presents low bioavailability and needs once or twice a day dosage. In order to improve its bioavailability, we used the host: guest strategy based on β-cyclodextrin (βCD). The results suggest that Los included in βCD showed a typical pulsatile release pattern after oral administration to rats, with increasing the levels of plasma of Los. In addition, the inclusion compound presented oral efficacy for 72 h, in contrast to Los alone, which shows antagonist effect for only 6 h. In transgenic (mREN2)L27 rats, the Los/βCD complex reduced blood pressure for about 6 d, whereas Los alone reduced blood pressure for only 2 d. More importantly, using this host: guest strategy, sustained release of Los for over a week via the oral route can be achieved without the need for encapsulation in a polymeric carrier. The proposed preformulation increased the efficacy reducing the dose or spacing between each dose intake.

Keywords:

• Inclusion compound
• controlled release
• pharmacokinetics
• absorption
• receptors

Acknowledgements

The authors acknowledge financial support by Brazilian agencies FAPEMIG, CAPES, CNPq, FINEP, INCT/Nanobiofar, Rede Nanofar, and Biolab-Sanus pharmaceutical company for the technology transfer contract assigned with the UFMG to scale up this technology.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Conselho Nacional de Desenvolvimento Científico e Tecnológico; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior; Financiadora de Estudos e Projetos; Fundação de Amparo à Pesquisa do Estado de Minas Gerais; INCT-Nanobiofar – Instituto Nacional de Ciência e Tecnologia Nanobiofarmacêutica.