Adwoa O. Nornoo

Oral microemulsions of paclitaxel: In situ and pharmacokinetic studies

The overall goal of this study was to develop cremophor-free oral microemulsions of paclitaxel (PAC) to enhance its permeability and oral absorption. The mechanism of this enhancement, as well as characteristics of the microemulsions relevant to the increase in permeability and absorption of the low solubility, low permeability PAC was investigated. Phase diagrams were used to determine the macroscopic phase behavior of the microemulsions and to compare the efficiency of different surfactant-oil mixtures to incorporate water. The microemulsion region on the phase diagrams utilizing surfactant-myvacet oil combinations was in decreasing order: lecithin: butanol: myvacet oil (LBM, 48.5%)>centromix CPS: 1-butanol: myvacet oil (CPS, 45.15%)>capmul MCM: polysorbate 80: myvacet oil (CPM, 27.6%)>capryol 90: polysorbate 80: myvacet oil (CP-P80, 23.9%)>capmul: myvacet oil (CM, 20%). Oil-in-water (o/w) microemulsions had larger droplet sizes (687-1010 nm) than the water-in-oil (w/o) microemulsions (272-363 nm) when measured using a Zetasizer nano series particle size analyzer. Utilizing nuclear magnetic resonance spectroscopy (NMR), the self-diffusion coefficient (D) of PAC in CM, LBM and CPM containing 10% of deuterium oxide (D(2)O) was 2.24x10(-11), 1.97x10(-11) and 0.51x10(-11) m(2)/s, respectively. These values indicate the faster molecular mobility of PAC in the two w/o microemulsions (CM and LBM) than the o/w microemulsion--CPM. The in situ permeability of PAC through male CD-IGS rat intestine was 3- and 11-fold higher from LBM and CM, respectively, than that from the control clinical formulation, Taxol (CE, cremophor: ethanol) in a single pass perfusion study. PAC permeability was significantly increased in the presence of the pgp/CYP3A4 inhibitor cyclosporine A (CsA). This enhancement may be attributed to the pgp inhibitory effect of the surfactants, oil and/or the membrane perturbation effect of the surfactants. The oral disposition of PAC in CM, LBM and CPM compared to CE was studied in male CD-IGS rats after a single oral dose (20 mg/kg). The area-under-the-curve of PAC in CM was significantly larger than LBM, CPM and CE. Oral microemulsions of PAC were developed that increased both the permeability and AUC of PAC as compared to CE.

Influence of internal structure and composition of liquid crystalline phases on topical delivery of paclitaxel

This study aimed to evaluate whether and how the internal structure and composition of liquid crystalline systems can be tailored to maximize paclitaxel cutaneous delivery. Liquid crystalline phases of water, Brij-97, and medium-chain mono/diglycerides (MCG) were characterized by polarized light microscopy. Lamellar phases containing 20% (w/w) water and MCG at 10% (LP-10) or 20% (LP-20), and a hexagonal phase (HP) with 45% water and 10% MCG were selected; paclitaxel was incorporated at 0.5% (w/w). Compared with drug solution in myvacet oil, LP-20 provided the highest paclitaxel cutaneous delivery (threefold), and LP-10 the highest transdermal delivery (fourfold). Using a fluorescent drug derivative [at 0.5%, (w/w)], we observed that penetration occurred through intact stratum corneum. To evaluate whether penetration results relate to drug release differences, paclitaxel self-diffusion coefficient (D) and in vitro release were studied. D was the highest in LP-20, but release from LP-20 and LP-10 was similar. The low D in HP was associated with the lowest drug release. As an index of efficacy, we assessed the cytotoxicity of paclitaxel-loaded LP-20 against fibroblasts. Cell viability was 1.3-2 times smaller with LP-20 than with drug solution. Our results demonstrate that LP-20 provides optimization of paclitaxel cutaneous delivery and efficient cytotoxicity.

Pharmacist involvement in medical missions: Planning, execution, and assessment

The motto of the Lloyd L. Gregory School of Pharmacy at Palm Beach Atlantic University is “pharmacy with faith,” and its vision is “excellence with character.” The school strives to develop “servant-leaders” who are patient care advocates fully committed to raising the standards of

Enhancement of transdermal delivery of progesterone using medium-chain mono and diglycerides as skin penetration enhancers.

We evaluated whether medium-chain mono and diglycerides (MCG) can be utilized to optimize the transdermal delivery of progesterone (PGT). MCG was studied at 10–70% (w/w) in propylene glycol (a polar solvent) or Myvacet oil (nonpolar solvent); PGT was used at 1% (w/w). The topical (to the skin) and transdermal (across the skin) delivery of PGT were evaluated in vitro using porcine ear skin. When incorporated in propylene glycol, MCG at 10% enhanced the topical and transdermal delivery of PGT by 2.5- and 7-fold, respectively. At 20–50%, topical delivery was further enhanced while transdermal delivery gradually returned towards baseline. At 70%, MCG enhanced neither the delivery to viable skin nor the transdermal delivery of PGT. Similar concentration-dependent effects were observed when MCG was incorporated in Myvacet oil, but their magnitudes were 2- to 3-fold smaller. The relative safety of MCG was assessed in cultured fibroblasts and compared to propylene glycol (regarded as safe) and sodium lauryl sulfate (moderate-to-severe irritant). Both MCG and propylene glycol were substantially less cytotoxic than sodium lauryl sulfate. We conclude that formulations containing 10% MCG in propylene glycol may be a simple and safe method to improve the transdermal delivery of progesterone and promote its use in hormone replacement therapy.

Stability of Vancomycin in Icodextrin Peritoneal Dialysis Solution

Background: Icodextrin is a glucose polymer used as an alternative osmotic agent in peritoneal dialysis (PD) solutions. There are few data regarding the long-term stability of vancomycin in icodextrin PD solution. Objective: To determine the chemical stability of vancomycin in icodextrin PD solution in polyvinyl chloride containers over a 7 day period at 4, 24, and 37 °C. Methods: Study samples were prepared by adding 2000 mg vancomycin HCl to commercially available 2.0 L bags of icodextrin 7.5% PD solution. Nine bags were prepared and stored in the following conditions: 3 under refrigeration (5 °C), 3 at room temperature (24 °C), and 3 at body temperature (37 °C). Samples were withdrawn from each bag immediately after preparation and at predetermined intervals over the subsequent 7 days. Solutions were visually inspected for precipitation, cloudiness, or discoloration at each sampling interval. Total concentration of vancomycin in dialysate fluid was determined by high performance liquid chromatography. Results: Under refrigeration, a mean ± SD of 99.7% ± 0.5% of the initial vancomycin concentration remained at 168 hours (7 days). At room temperature, 97.5% ± 3.4% remained at 168 hours. At body temperature, 94.3% ± 3.9% remained at 24 hours. Stability was not assessed beyond these time points. Conclusions: Premixed vancomycin-icodextrin PD solutions, whether stored refrigerated or at room temperature, were found to be stable for up to 7 days. However, we recommend that these solutions be kept refrigerated whenever possible. Solutions stored at body temperature were stable for up to 24 hours, permitting the practice of prewarming solutions prior to administration.

Impact of the chemical and physical stability of ketoprofen compounded in various pharmaceutical bases on its topical and transdermal delivery

Abstract Increasing demands for individualized drug treatment has led to an increase in the practice of compounded medications. In this study, we determined the impact of the chemical and physical stability of ketoprofen (10%w/w) cream on its topical/transdermal delivery over a 6-month period. The shelf life of ketoprofen at 25 °C in the pharmaceutical bases LipoDerm and LipoBase (109.94 and 85.9 days) was significantly longer than that in Pluronic Lecithin Organogel (PLO; 44.81 days), justifying extending its beyond use date (BUD) from 30 (USP37/NF32) to at least 60 days in LipoDerm and LipoBase. All the creams evaluated exhibited shear-thinning flow behavior with moderate thixotropy, while the flow properties for LipoBase and PLO creams were altered at storage times greater than 90 days. The percentage of ketoprofen permeated through porcine ear skin was 13.7, 19.1 and 12.7% of the dose from LipoDerm, LipoBase and PLO, respectively and decreased 2- to 3-fold after 28 days of storage. Flux ranging from 85.3 to 446.7 µg/cm2/h and topical delivery, on the other hand, were not influenced by storage duration past 28 days. In conclusion, this study justifies extending the BUD of ketoprofen in LipoDerm and LipoBase to 60 days if used for topical delivery only.

A Floating Pharmacy on Lake Tanganyika

The Gregory School of Pharmacy at Palm Beach Atlantic University recently partnered with Operation Mobilization, Africa, on a medical mission to Mpulungu, Zambia, in May 2010. One of our alumni was the catalyst for this partnership. Talk about uncommon partners, common ground, and changing lives! Our team comprised a pharmaceutics faculty with expertise in formulation development and compounding, a pharmacy practice faculty specialized in pharmacotherapy and with expertise in infectious diseases, a community pharmacist with expertise in HIV/AIDS, a retail pharmacist, a physical therapist, 7 student pharmacists, and an electrical engineer. We met every other week for 6 months to prepare the students and order medications and supplies. All team members were encouraged to follow the recommendations of the Centers for Disease Control and Prevention regarding health information for travelers to Zambia, which include malaria prophylaxis, hepatitis A, hepatitis B, typhoid, and rabies vaccines in addition to routinely recommended vaccines and general principles to prevent travelers’ diarrhea. After taking two 8-hour international flights, we arrived in Lusaka, the capital of Zambia. We spent the first 2 nights at a guest house, where we gathered all the medical supplies we brought from home: multivitamins, oral rehydration solutions, antacids, antimotility agents, antimicrobials, analgesics and antipyretics, allergy and cough products, wound care supplies, and various topical preparations. We had a great time for bonding activities and fellowship together. The third day, we woke up early in the morning to travel to Mpulungu . . . sounds like ‘‘Oompa-Loompas’’ from the movie Willy Wonka and the Chocolate Factory . . . but Mpulungu is actually a small coastal town in the northern part of the country. The 16-hour bus drive was grueling and we were surprised that we had to pay anywhere from 500 to 1000 kwachas to use the restrooms along the way, which is roughly the equivalent of 1 to 2 dimes! It was evening by the time we reached our destination, and we were exhausted but excited to meet the missionaries who welcomed us with a great meal, and we quickly learned from them the basics of interacting with the locals and the history behind the floating pharmacy on Lake Tanganyika. Shared by Burundi, Congo, Tanzania, and Zambia, Lake Tanganyika holds the unique distinction of being the world’s longest and second deepest freshwater lake. It is fascinating not only by its sparkling turquoise water and virgin green surrounding but also by the people who live around its shore. It appears that the London Missionary Society had originally commissioned a 54-foot steamboat ‘‘SS Good News’’ built in 1882 to serve the medical need of the people in the area after a plea by Dr David Livingstone. The fact that the hull of the steamboat lies abandoned in Kituta Bay east of Mpulungu led to the vision that the missionaries had to convert a former luxury yacht into ‘‘Good News II,’’ the floating pharmacy on Lake Tanganyika (Figure 1). We visited 2 fishing communities along the lake, where houses were mainly huts with thatched roofs and toilets were deep holes dug in the ground known to the locals as the ‘‘long drop.’’ There was no running water and no electricity. We played with the children who were very excited to see visitors and met with the tribe leaders and listened to their concerns. We were especially moved by the evident lack of medical care and happy to be able to stock the floating pharmacy with medicines and supplies. We also visited the only local hospital and rounded with the only medical doctor in Mpulungu. As clinical pharmacists and student pharmacists, we learned from the doctor about the most frequently encountered disease states: gastrointestinal infections, AIDS, opportunistic infections, tuberculosis, and malaria. We offered recommendations on how to treat patients with these infections based on current practice guidelines and using the limited pharmacy formulary. We also offered recommendations on how to monitor the efficacy and safety of commonly prescribed antimicrobials, taking into consideration the limited available laboratory tests. There was an outbreak of cholera in the area and everyone was worried about getting infected. We discussed with the medical team some infection control strategies to contain the outbreak and the available treatment options for cholera. We spent the last days of our medical mission with the missionaries. We toured the school and the orphanage that they built and supplied the teachers with over-the-counter products for the children they serve. We educated the nurse and the medical officer about the judicious and appropriate use of the