Analysis of docosanol using GC/MS: Method development, validation, and application to ex vivo human skin permeation studies.

Docosanol is the only US Food and Drug Administration (FDA) approved over-the-counter topical product for treating recurrent oral-facial herpes simplex labialis. Validated analytical methods for docosanol are required to demonstrate the bioequivalence of docosanol topical products. A gas chromatography/selected ion monitoring mode mass spectrometry (GC/SIM-MS) method was developed and validated for docosanol determination in biological samples. Docosanol and isopropyl palmitate (internal standard) were separated on a high-polarity GC capillary column with (88% cyanopropy)aryl-polysiloxane employed as the stationary phase. The ions of m/z 83 and 256 were selected to monitor docosanol and isopropyl palmitate, respectively; the total run time was 20 min. The GC/SIM-MS method was validated in accordance with US FDA guidelines, and the results met the US FDA acceptance criteria. The docosanol calibration standards were linear in the 100-10000 ng/mL concentration range (R 2>0.994). The recoveries for docosanol from the receptor fluid and skin homogenates were >93.2% and >95.8%, respectively. The validated method was successfully applied to analyze ex vivo human cadaver skin permeation samples. On applying Abreva® cream tube and Abreva® cream pump, the amount of docosanol that penetrated human cadaver skin at 48 h was 21.5 ± 7.01 and 24.0 ± 6.95 ng/mg, respectively. Accordingly, we concluded that the validated GC/SIM-MS was sensitive, specific, and suitable for quantifying docosanol as a quality control tool. This method can be used for routine analysis as a cost-effective alternative to other techniques.

Thermosensitive in situ liposomal gels loaded with antimicrobial agent for oral care in critically ill patients.

Aim: A novel thermosensitive in situ gel loaded with meropenem (MP) liposomes was designed to improve retention in the oral cavity as a prophylactic measure to prevent ventilator-acquired pneumonia in critically ill patients. Methodology & results: Meropenem liposomes were incorporated into poloxamer 407 gels and gamma irradiated. Mean size of liposome was 247 nm, polydispersity index < 0.3 and zeta potential >-25 mV; properties remained unaltered even post sterilization. Permeation study revealed that 75.26% and 34% of MPs were released from MP in situ gel and MP in situ liposomal gel, respectively. The relation between viscosity (cp) and shear rate (1/s) indicate that in situ gels exhibited non-Newtonian behavior at 37°C. The study using Pseudomonas aeruginosa confirmed the antimicrobial activity of meropenem. Conclusion: Prolonged in situ residence, because of rapid gelation process enables an easy administration of meropenem as liposomal suspension in critically ill patients.

Delivery of brain-derived neurotrophic factor via nose-to-brain pathway.

PURPOSE: To investigate the plausibility of delivering brain-derived neurotrophic factor (BDNF) to brain via nose-to-brain pathway using chitosan as barrier-modulating agent. METHODS: Effect of different viscosity grades chitosan at different concentrations on permeation of fluorescein isothio-cyanate dextran (FD 40 K) across bovine olfactory mucosa was studied using Franz diffusion cells. Medium viscosity chitosan was used to carry out permeation studies of BDNF. Pharmacokinetic and pharmacodynamic studies were carried out in Sprague dawley rats upon intranasal/i.v administration of different formulations. RESULTS: Medium viscosity chitosan more efficiently enhanced permeation of FD 40 K across olfactory mucosa compared to other grades. In case of BDNF, medium viscosity chitosan (0.25% w/v) enhanced permeation ~14-fold over control (18.78 ± 16.69 ng/cm(2)). Brain bioavailability of rats administered intranasally with BDNF solution containing chitosan was significantly enhanced ~13-fold compared to rats administered with same concentration of BDNF solution without chitosan. In rats subjected to immobilization stress, BDNF solution containing chitosan significantly decreased immobility time. CONCLUSIONS: Intranasal formulations containing chitosan as barrier-modulating agent significantly enhanced brain bioavailability of BDNF. Delivery of BDNF was found to counteract stress-induced depression in rats.