Analysis of in vivo absorption of didanosine tablets in male adult dogs by HPLC

Abstract

Didanosine is an effective antiviral drug in untreated and antiretroviral therapy-experienced patients with Human Immunodeficiency Virus (HIV). An automated system using on-line solid extraction and High Performance Liquid Chromatography (HPLC) with ultraviolet (UV) detection was developed and validated for pharmacokinetic analysis of didanosine in dog plasma. Modifications were introduced on a previous methodology for simultaneous analysis of antiretroviral drugs in human plasma. Extraction was carried out on C18 cartridges, with high extraction yield as stationary phase, whereas mobile phase consisted of a mixture of 0.02 M potassium phosphate buffer, acetonitrile (KH2PO4: acetonitrile: 96:4, v/v) and 0.5% (w/v) of heptane sulphonic acid. The pH was adjusted to 6.5 with triethylamine. All samples and standard solutions were chromatographed at 28 °C. For an isocratic run, the flux was 1.0 mL/min, detection was at 250 nm and injected volume was 20 μL. The method was selective and linear for concentrations between 50 and 5000 ng/mL. Drug stability data ranged from 96% to 98%, and limit of quantification was 25 ng/mL. Extraction yield was up to 95%. Drug stability in dog plasma was kept frozen at −20 °C for one month after three freeze–thaw cycles, and for 24 h after processing in the auto sampler. Assay was successfully applied to measure didanosine concentrations in plasma dogs.

Preparation of gastro-resistant pellets containing chitosan microspheres for improvement of oral didanosine bioavailability

“…Briefly, the microspheres were formed by dropping an aqueous solution composed of TPP (2 g/L), magnesium hydroxide (6 g/L) and didanosine (39 g/L), to a chitosan aqueous solution (2.0% w/v) previously acidified with acetic acid. The solutions were mixed under stirring (2000 rpm) at 25 °C [5] , [13] , [14] .…”

“…Furthermore, the lower bioavailability makes didanosine a good candidate for extended release formulations. For pharmacokinetic analysis of didanosine in vivo, we have recently published our first attempt in validating an automated system using on-line solid extraction and high performance liquid chromatography (HPLC) with ultraviolet (UV) detection [5] .…”

Pediatric Drug Development: Reviewing Challenges and Opportunities by Tracking Innovative Therapies

“…Abbreviations: area under the curve (AUC), the maximum observed concentration of the drug collected in bodily material from subjects in a clinical study (Cmax), clearance (CL), Intravenous (i.v), Intrathecal (I/T), time needed to reach the maximum concentration or time to Cmax (Tmax), half-life, is the time it takes for half the drug concentration to be eliminated (T 1/2 ). To make chitosan granules containing didanosine incorporated in chitosan microspheres, to facilitate handling and deglutition [177] Table 5. Completed clinical trials using chitosan.…”

Polímeros usados como sistemas de transporte de princípios ativos

“…Vantagens desta classe de polímeros incluem a bioadesão a mucosas como ocular, nasal, urinária, gastrointestinal e vaginal, proporcionando biocompatibilidade, biodegradabilidade e, por conseguinte, maior biodisponibilidade dos princípios ativos administrados. A desvantagem é a variação que sofrem em relação aos lotes devido ao processo de obtenção e purificação [20,21] .…”