Liquid chromatographic-mass spectrometric method for determination of drug content uniformity of two commonly used dermatology medications in a split-tablet dosage form

Purpose: To develop and validate a simple, efficient and reliable Liquid chromatographic-mass spectrometric (LC-MS/MS) method for the quantitative determination of two dermatological drugs, Lamisil® (terbinafine) and Proscar® (finasteride), in split tablet dosage form. Methods: Thirty tablets each of the 2 studied medications were randomly selected. Tablets were weighed and divided into 3 groups. Ten tablets of each drug were kept intact, another group of 10 tablets were manually split into halves using a tablet cutter and weighed with an analytical balance; a third group were split into quarters and weighed. All intact and split tablets were individually dissolved in a water: methanol mixture (4:1), sonicated, filtered and further diluted with mobile phase. Optimal chromatographic separation and mass spectrometric detection were achieved using an Agilent 1200 HPLC system coupled with an Agilent 6410 triple quadrupole mass spectrometer. Analytes were eluted through an Agilent eclipse plus C8 analytical column (150 mm × 4.6 mm, 5 μm) with a mobile phase composed of solvent A (water) containing 0.1% formic acid and 5mM ammonium formate pH 7.5, and solvent B (acetonitrile mixed with water in a ratio A:B 55:45) at a flow rate of 0.8 mL min-1 with a total run time of 12 min. Mass spectrometric detection was carried out using positive ionization mode with analyte quantitation monitored by multiple reaction monitoring (MRM) mode. Results: The proposed analytical method proved to be specific, robust and adequately sensitive. The results showed a good linear fit over the concentration range of 20 - 100 ng mL-1 for both analytes, with a correlation coefficient (r2) ≥ 0.999 and 0.998 for finasteride and terbinafine, respectively. Following tablet splitting, the drug content of the split tablets fell outside of the proxy USP specification for at least 14 halves (70 %) and 34 quarters (85 %) of FIN, as well as 16 halves (80 %) and 37 quarters (92.5 %) of TBN. Mean weight loss, after splitting, was 0.58 and 2.22 % for FIN half- and quarter tablets, respectively, and 3.96 and 4.09 % for TBN half- and quarter tablets,respectively. Conclusion: The proposed LC-MS/MS method has successfully been used to provide precise drug content uniformity of split tablets of FIN and TBN. Unequal distribution of the drug on the split tablets is indicated by the high standard deviation beyond the accepted value. Hence, it is recommended not to split non-scored tablets especially, for those medications with significant toxicity

Magnetic Nanoparticle-based Targeted Drug Delivery for Treatment of Neuro-AIDS and Drug Addiction

Brain is one of the safe sanctuaries for HIV and, in turn, continuously supplies active viruses to the periphery. Additionally, HIV infection in brain results in several mild-to-severe neuro-immunological complications termed neuroAIDS. One-tenth of HIV-infected population is addicted to recreational drugs such as opiates, alcohol, nicotine, marijuana, etc. which share common target-areas in the brain with HIV. Interestingly, intensity of neuropathogenesis is remarkably enhanced due to exposure of recreational drugs during HIV infection. Current treatments to alleviate either the individual or synergistic effects of abusive drugs and HIV on neuronal modulations are less effective at CNS level, basically due to impermeability of therapeutic molecules across blood-brain barrier (BBB). Despite exciting advancement of nanotechnology in drug delivery, existing nanovehicles such as dendrimers, polymers, micelles, etc. suffer from the lack of adequate BBB penetrability before the drugs are engulfed by the reticuloendothelial system cells as well as the uncertainty that if and when the nanocarrier reaches the brain. Therefore, in order to develop a fast, target-specific, safe, and effective approach for brain delivery of anti-addiction, anti-viral and neuroprotective drugs, we exploited the potential of magnetic nanoparticles (MNPs) which, in recent years, has attracted significant importance in biomedical applications. We hypothesize that under the influence of external (non-invasive) magnetic force, MNPs can deliver these drugs across BBB in most effective manner. Accordingly, in this dissertation, I delineated the pharmacokinetics and dynamics of MNPs bound anti-opioid, anti-HIV and neuroprotective drugs for delivery in brain. I have developed a liposome-based novel magnetized nanovehicle which, under the influence of external magnetic forces, can transmigrate and effectively deliver drugs across BBB without compromising its integrity. It is expected that the developed nanoformulations may be of high therapeutic significance for neuroAIDS and for drug addiction as well.

Effect of the Supplemental Nutrition Assistance Program (SNAP) and Nutrition Education on Nutrition and Health Outcomes of HIV+ Individuals

Factors associated with and barriers to participation in Supplemental Nutrition Assistance Program (SNAP) and the effect participation has on food security, nutrition status, disease status and quality of life was investigated in a cross-sectional study including 175 HIV infected individuals. In addition, the effect of a targeted nutrition education on nutrition knowledge, readiness to dietary behavior change, nutrition status, disease status and quality of life was also investigated among a subset of the population (N = 45) in a randomized clinical control trial. SNAP participation rate was 70.3%, similar to the State of Florida and national participation rates. SNAP participation was positively and independently associated with being born in the US (P < 0.001), having monthly income less than $1000 (P = 0.006), and receiving antiretroviral treatment (P < 0.001). Participation barriers include denial of participation by program, recent incarceration, living in a shelter where participation is not allowed and unawareness of eligibility status. In regression analyses, SNAP participation was not significantly associated with improved food security, nutrition status, disease status and health related quality of life (HRQOL). Over half (56%) of the population experienced food insecurity and had inadequate intakes of half of the nutrients assessed. Illicit drug, alcohol and cigarette use were high in this population (31%, 55% and 63% respectively), and affected food security, nutrients intake, disease status and HRQOL. The nutrition education intervention resulted in a trend towards improvements nutrition knowledge, self-efficacy, and readiness to change without impacting nutrition status, disease state and quality of life. Food insecurity and other nutrition related issues, with implications for treatment, management and cost of HIV disease, continue to plague infected individuals living in poverty. More resources, including food and nutrition programs, specifically targeted towards this population are needed to address these issues.

Life history of a native emydid turtle (Malaclemys terrapin centrata) on the remote oceanic islands of Bermuda

Diamondback terrapins (Malaclemys terrapin) are native to the remote oceanic islands of Bermuda and presently inhabit only four small brackish water ponds on a private golf course. The life history of this species is poorly understood on Bermuda and so the aim of this study was to fill these knowledge gaps, to compare the results with what is known from other areas in the North American range, and to inform the development of a local management plan. The results of a mark-recapture census revealed that ca. 100 individuals ≥81 mm straight carapace length live on Bermuda, of which nearly half (48.5%) were considered sexually mature. The population is dominated by females (sex ratio 2.9:1) and annual recruitment over the three year period was found to be extremely low (approximately two terrapins). Female diamondback terrapins in Bermuda nest almost exclusively within a limited number of sand bunkers on the golf course. Nesting commenced in late March or early April and ended in late August. Peak oviposition was observed in May and June. Clutch size averaged 5.1 eggs (range 0-10; SD 2.4) and the incubation period averaged 61.8 days (range 49-83; SD 10.5). Delayed emergence was documented, with 43.8% of the hatchlings remaining in their natal nests over the winter months. The mean annual hatching success rate was determined to be 19% (range 17.6-21; SD 1.9). Radio-telemetry was used to investigate the movements and survivorship of postemergent hatchling diamondback terrapins. The results indicated that mangrove swamps and grass-dominated marshes adjacent to the ponds are important developmental habitats for hatchlings. Yellow-crowned night herons (Nyctanassa violacea) were found to be significant predators of small terrapins during spring emergence. Small aquatic gastropods comprised 66.7% of the faecal samples analysed from the Bermudian population. Scavenged fish and vertebrate animal remains, terrestrial arthropods, polychaete worms and bivalves were consumed in lesser amounts. Sediment from the pond environment was found in 74% of the faecal samples analysed and is believed to have been incidentally ingested while foraging for the small benthic gastropods. Eco-toxicological analyses of the pond sediment, prey and terrapin eggs showed that the Bermudian diamondback terrapins live and feed in wetland habitats characterised by chronic, multifactorial contamination; principally total petroleum hydrocarbons, polycyclic aromatic hydrocarbons and a variety of heavy metals. This study found that some of those contaminants are accumulating in the gastropod prey as well as being transferred to terrapin eggs. This may be reducing the incidence of successful embryonic development for this species in Bermuda and may likely contribute to the observed low hatching rates. These collective findings indicate that the Bermudian population is very vulnerable to local extirpation.