Prevalence, Scope and Quality of Extemporaneous Medications in Selected Healthcare Facilities and Implications for Pharmacy Practice.

Background: Extemporaneous compounding is the preparation of medicines for individual patients when no commercially available authorized form exists. Unlike registered medications, these products are not subjected to various tests for quality by Regulatory Authorities. Data on compounded medications in Ghana is currently inadequate or unavailable. There is the need to collate data that can be used to influence policy and to regulate preparation of extemporaneous products. Aim: To establish the prevalence, scope and quality of extemporaneously compounded medicines at selected hospitals in Accra, Ghana. Methodology: Prescriptions presented at the pharmacies in selected hospitals were reviewed to determine the requests that needed to be extemporaneously prepared as well as the prevalence and the scope of formulations. Three of the most frequently compounded medications were procured and subjected to microbial contamination tests using the pour plate method followed by differential tests if microbes were present. Content analysis of the active ingredients was determined using High Performance Liquid Chromatography (HPLC). Results: 641 requests comprising 49 different extemporaneous products were collated from the hospitals studied. Hydroxyurea, furosemide and spironolactone suspensions were the three most frequently prescribed. Patients aged from 0-2 years had majority of the prescriptions. Conclusion: A population of patients still exist who depend on compounding for their drug needs. 49 different formulations were prepared at one of the hospitals visited. Samples of products analyzed were of good quality.

Transdermal Immunization with Microparticulate RSV-F Virus-like Particles Elicits Robust Immunity.

No approved vaccines against respiratory syncytial virus (RSV) infections exist to date, due to challenges arising during vaccine development. There is an unmet need to explore novel approaches and a universal strategy to prevent RSV infections. Previous studies have proven the immune efficacy of virus-like particles (VLPs) consisting of RSV fusion (F) protein, yielding a highly immunogenic RSV-F VLP subunit vaccine. In this study, RSV-F VLP (with or without MPL®) was added to a polymer mix and spray-dried, forming microparticles. The formulations were transdermally administered in C57BL/6 mice to evaluate vaccine efficacy. The transdermal delivery of RSV-F VLP + MPL® was more effective in clearing lung viral loads and preventing weight loss after RSV challenge. At the cellular level, MPL® augmented the vaccine response in microparticulate form, which was evidenced by higher serum and lung antibody titers, and lower lung viral titers in the vaccinated groups. These preliminary results validate the effectiveness of the RSV-F VLP microparticulate vaccine via the transdermal route due to its potential to trigger robust immune responses.

Dendritic cell activation by a micro particulate based system containing the influenza matrix-2 protein virus-like particle (M2e VLP).

M2e VLP was previously described as a vaccine that incorporates the extracellular region of the matrix 2 protein (M2e), which is highly conserved amongst all the strains of influenza. In this study, we analyzed activation status of dendritic cells (DCs) after exposure to M2e VLP, stimulating DCs with M2e VLP and co-culturing the stimulated DCs with T cells to observe innate and adaptive immune responses. The M2e VLP microparticle was prepared by encapsulating into a polymer matrix using the one-step spray drying method. Adjuvants Alhydrogel®, MPL-A® or AddavaxTM were used to enhance the DC stimulatory effects by the M2e VLP microparticle. The M2e VLP microparticle yield was found to be 92% and the encapsulation yield was around 84% with a size of approximately 2.78 µm. There was no short-term cytotoxicity found in DCs and macrophages with concentrations up to 1500 µg/mL of M2e VLP microparticle, however long-term exposure resulted in 25% decrease in viability of cells with concentrations more than or equal to 500 µg/mL. The M2e VLP microparticle vaccine with Alhydrogel® and MPL-A® induced high levels of TNFα in both DCs and macrophages. The high levels of MHC I, II, CD28, B7-1, ICAM-1, LFA-1 expression and IL-12 release in the M2e VLP microparticle group with Alhydrogel® suggests that the M2e VLP vaccine with this adjuvant activated T cells via the Th2 pathway. The increased expression of MHC I, II, CD40, CD154, ICAM-1 and LFA-1 on DCs and the release of IL-12 in the M2e VLP microparticle culture of DCs with MPL-A® demonstrated that the M2e VLP vaccine with this adjuvant activated T cells via the Th1 pathway. The decrease in fluorescence in the Alhydrogel® and MPL-A® group illustrates the proliferation of T cells took place following exposure of DCs to the M2e VLP microparticle with these adjuvants. The M2e VLP microparticle exhibited higher stimulatory responses of DCs than the M2e VLP in suspension. Furthermore, the presence of Alhydrogel® and MPL-A® enhanced the stimulatory effects of DCs by the M2e VLP microparticle (MP) vaccine.

Transdermal Vaccination with the Matrix-2 Protein Virus-like Particle (M2e VLP) Induces Immunity in Mice against Influenza A Virus.

In this study, our goal was to utilize the extracellular domain matrix-2 protein virus-like particle (M2e VLP) that has been found to be highly conserved amongst all strains of influenza and could serve as a potential vaccine candidate against influenza. Previous studies have demonstrated that the VLP of the M2e showed increased activation of innate and adaptive immune responses. Therefore, to further explore its level of efficacy and protection, this vaccine was administered transdermally and tested in a pre-clinical mouse model. The M2e VLP was encapsulated into a polymeric matrix with the addition of Alhydrogel® and Monophosphoryl Lipid-A (MPL-A®), together referred to as AS04. The M2e VLP formulations induced IgG titers, with increased levels of IgG1 in the M2e VLP MP groups and further elevated levels of IgG2a were found specifically in the M2e VLP MP Adjuvant group. This trend in humoral immunity was also observed from a cell-mediated standpoint, where M2e VLP MP groups showed increased expression in CD4+ T cells in the spleen and the lymph node and high levels of CD8+ T cells in the lymph node. Taken together, the results illustrate the immunogenic potential of the matrix-2 protein virus-like particle (M2e VLP) vaccine.

Chitosan-Coated Hydroxypropylmethyl Cellulose Microparticles of Levodopa (and Carbidopa): In Vitro and Rat Model Kinetic Characteristics.

BACKGROUND: Parkinson's disease is a neurodegenerative disorder, and a major cause of disability. Levodopa, a prodrug of dopamine, remains the gold standard in the pharmacological management of Parkinson's disease. Despite several attempts to improve the clinical efficacy of levodopa, new oral levodopa formulations are needed to overcome irregular absorption and variable plasma concentrations. OBJECTIVE: The aim of this study was to evaluate the in vitro and in vivo kinetic properties of chitosan-coated hydroxypropylmethyl cellulose microparticles of levodopa (and carbidopa). METHODS: Microparticles were formulated by encapsulating levodopa powder in chitosan-coated hydroxypropylmethyl cellulose using the spray-drying method. Levodopa microparticles were evaluated for size, zeta potential, drug loading capacity, encapsulation efficiency and in vitro release. In evaluating in vivo pharmacokinetics, Sprague Dawley rats were administered either levodopa/carbidopa powder, levodopa/carbidopa microparticles, or Sinemet CR (a controlled release formulation of levodopa/carbidopa). The dose of respective formulations administered was 20/5 mg/kg; 20 mg levodopa combined with 5 mg carbidopa per kilogram body weight of animals. Treatments were administered via the oral route every 12 hours. Blood samples were collected after predetermined times following the third dose. Plasma was obtained from blood collected, and levodopa levels determined by HPLC. Pharmacokinetic parameters, including Cmax, Tmax, AUC, and t½ of the various formulations, were estimated. RESULTS: The mean (SD) size of levodopa microparticles was 0.5 (0.05) µm with polydispersity index of 0.41 and a zeta potential of 10.8 mV. Of the expected 20% drug loading, the actual drug loading capacity of levodopa microparticles was found to be 19.1%, giving an encapsulation efficiency of 95.7%. The in vitro release kinetics of levodopa microparticles showed a controlled and sustained release, with about 80% release occurring after 12 hours. In vivo pharmacokinetic studies showed that rats administered levodopa/carbidopa microparticles had greater AUC (612.7 [17.42] ng.h/mL) and higher Cmax (262.4 [38.86] ng/mL) compared with Sinemet CR: AUC 354.7 (98.09) ng.h/mL and Cmax 95.5 (20.87) ng/mL. However, Sinemet CR had a much longer half-life (6.1 [2.58] hours) compared with levodopa/carbidopa microparticles (2.0 [0.31] hours). CONCLUSIONS: Findings from this study suggest that chitosan-coated hydroxypropylmethyl cellulose microparticles of levodopa/carbidopa may give relatively high levels of levodopa in circulation. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX)© 2020 Elsevier HS Journals, Inc.

Quinine Sulphate Microparticles as Treatment for Leishmaniasis.

BACKGROUND: Leishmaniasis is a neglected tropical disease caused by the Leishmania parasite and transmitted by the female phlebotomine sandfly. The disease can affect the skin (least fatal) or internal organs (most fatal). Current treatment options for leishmaniasis have a number of adverse effects, and there appears to be resistance by the protozoan parasite (Leishmania spp.). Reports suggest that quinine sulphate, not indicated for leishmaniasis, is effective in killing the Leishmania parasite. Indeed, the efficacy of any drug is dependent on the concentration at the target site, which is also almost dependent on drug formulation. The current study assessed the pharmacokinetic profile of the microparticulate formulation of quinine sulphate and its in vitro and in vivo efficacy against Leishmania donovani. METHODS: Quinine sulphate was encapsulated in bovine serum albumin by the spray-drying method. Quinine sulphate microparticles were evaluated for size, zeta potential, drug content, encapsulation efficiency, and in vitro release properties. Afterwards, the pharmacokinetic characteristics of quinine sulphate microparticles were estimated and in vivo efficacy studies were also conducted. RESULTS: The size range of the quinine sulphate microparticles was between 2.0 and 5.0 µm. Microparticles had an average zeta potential of -35.2 mV and an encapsulation efficiency of 94.5%. Also, C max, t 1/2, and AUC were all significantly desirable for quinine sulphate microparticles compared to the drug powder. Quinine sulphate microparticles significantly reduced parasite load in rat organs than amphotericin B. CONCLUSION: Overall, quinine sulphate microparticles had better pharmacokinetic profile and showed higher efficacy against Leishmania donovani parasites in vivo. Thus, quinine sulphate microparticles have the potential, especially, in treating visceral leishmaniasis.

Complementary and Alternative Medicine Use for Primary Dysmenorrhea among Senior High School Students in the Western Region of Ghana.

BACKGROUND: Dysmenorrhea is a major gynaecological complaint among females who have reached menarche. It is one of the major causes of absenteeism of females from schools and at the workplaces resulting in loss of productive working hours and work efficiency. Owing to socioeconomic and cultural differences, females from different backgrounds perceive and manage dysmenorrhea differently. Little is known about the use of complementary and alternative medicines (CAM) in the management of this condition by females in senior high schools in Ghana. Thus, this study sought to assess the use of CAM in the management of dysmenorrhea among female students in two senior high schools in Ghana. METHODS: A school-based cross-sectional study using a quantitative approach was conducted on a total of 478 female students attending Archbishop Porter Girl's Secondary School and Mporhor Senior High School. Information on the sociodemographic characteristics, lay representations of dysmenorrhea, pain intensity and severity, quality of life, self-management, and the use of CAM in the management of dysmenorrhea were obtained. The data were analysed using SPSS. RESULTS: 79.3% of the students used some form of CAM to manage dysmenorrhea. Of CAM users, 32% were utilizing mind-body medicine such as endurance and relaxation, 31% used the whole and alternative medicine such as the hot water therapy, 15% used biological-based medicine such as herbal products, and 22% used the manipulative and body-based systems such as exercises. Various CAM methods and products were perceived to be effective in relieving the pain and discomfort associated with dysmenorrhea in about 90% of the participants who used them. Significant associations were reported for pain severity and quality of life (QoL). CONCLUSIONS: This study has demonstrated that the female students experiencing dysmenorrhea employ various CAM remedies in its management. Therefore, there is the need for education on the right management of dysmenorrhea to ensure that safe and efficacious CAM products and methods are used by adolescent female students.

Assessment of formulated amodiaquine microparticles in Leishmania donovani infected rats.

The aim of this study was to formulate, characterise and evaluate the activity of amodiaquine microparticles against Leishmania donovani. Microparticles were formulated by encapsulating the drug in bovine serum albumin using the spray-dryer method. The microparticles were evaluated for size, zeta potential, drug content, encapsulation efficiency and in vitro release profile. The size range of the microparticles formulated was between 1.9 and 10 µm with an average zeta potential of -25.5 mV. Of the expected 20% drug loading, an average of 18.27% was obtained giving an encapsulation efficiency of 91.35%. Pharmacokinetic profile of amodiaquine improved with microencapsulation of the drug with Cmax, AUC0→48 and t1//2 all significantly higher than amodiaquine solution. Amodiaquine microparticles showed an overall higher bioavailability and hence were more effective in eliminating intra-tissue parasites than the drug solution. It would therefore be expected that the formulated microparticles will be more effective in treating visceral leishmaniasis.