Formulation, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles.

CONTEXT: Formulation, characterization, in vitro and in vivo evaluation of halofantrine-loaded solid lipid microparticles (SLMs). OBJECTIVE: The objective of the study was to formulate and evaluate halofantrine-loaded SLMs. MATERIALS AND METHODS: Formulations of halofantrine-loaded SLMs were prepared by hot homogenization and thereafter lyophilized and characterized using particle size, pH stability, loading capacity (LC) and encapsulation efficiency (EE). In vitro release of halofantrine (Hf) from the optimized SLMs was performed in SIF and SGF. In vivo study using Peter's Four day suppressive protocol in mice and the mice thereafter subjected to histological studies in kidney and liver. RESULTS: Results obtained indicated that EE of 76.32% and 61.43% were obtained for the SLMs containing 7% and 3% of Hf respectively. The SLMs loaded with 3% of Hf had the highest yield of 73.33%. Time-dependent pH stability analysis showed little variations in pH ranging from 3.49 ± 0.04 to 4.03 ± 0.05. DISCUSSION: The SLMs showed pH-dependent release profile; in SIF (43.5% of the drug for each of H2 and H3) compared with SGF (13 and 18% for H2 and H3 respectively) after 8 h. The optimized SLMs formulation and Halfan® produced a percentage reduction in parasitemia of 72.96% and 85.71% respectively. The histological studies revealed that the SLMs formulations have no harmful effects on the kidney and liver. CONCLUSION: SLMs formulations might be an alternative for patients with parasitemia as there were no harmful effects on vital organs of the mice.

Evaluation of dika wax-soybean oil-based artesunate-loaded lipospheres: in vitro-in vivo correlation studies.

OBJECTIVES: To formulate and evaluate artesunate-loaded lipospheres and study the in vitro-in vivo correlations (IV-IVC). MATERIALS AND METHODS: Lipospheres were formulated by melt homogenisation using structured lipid matrices consisting of (1:3 and 1:6) soybean oil and dika wax and were characterised in vitro and in vivo. RESULTS: The small angle X-ray diffraction (SAXD) results of the lipid matrices showed prominent reflection at 2θ = 2.49°, d = 3.55 Å while, wide angle X-ray diffraction (WAXD) showed prominent reflection at 2θ = 20.83°, d = 0.42 Å. Lipospheres had maximum encapsulation efficiency of 80%, showed no significant decrease in pH with time (p < 0.05), and had sustained release properties. The ratio of the area under the curve (AUC) of the lipospheres and the tablets gave bioavailability enhancement factor of 2.108. CONCLUSION: Artesunate-loaded lipospheres could be used orally or parenterally once daily, for the treatment of malaria.

Clinical administration of microneedles: skin puncture, pain and sensation.

Injections using hypodermic needles cause pain, discomfort, localised trauma and apprehension. Additionally, careful use and disposal of needles is required to avoid transmission of blood-borne pathogens. As an alternative, microneedles can facilitate drug delivery without significantly impacting on pain receptors or blood vessels that reside beneath the skin outer layers. In this study we aim to determine the pain and sensory response to the application of wet-etch silicon microneedles, when used in such a way as to reliably penetrate skin, and provide a preliminary indication of how skin responds to microneedle injury with time. Twelve subjects received single-blinded insertions of a 25-G hypodermic needle and two microneedle arrays (36 needles of 180 and 280 mum height). The optimal method for microneedle application was determined in a pilot study. Pain intensity was scored using a visual analogue scale (VAS) and sensory perception determined using an adapted McGill Pain Questionnaire Short Form. Skin penetration was determined by external staining and measurement of trans-epidermal water loss (TEWL). Mean VAS scores, verbal descriptions and questionnaire responses showed that the 180 and 280 mum microneedles caused significantly less pain and discomforting sensation in participants than the hypodermic needle. Methylene blue staining and TEWL analysis confirmed that microchannels were formed in the skin following microneedle application. Evidence of microchannel repair and resealing was apparent at 8-24 h post-application. In summary, this study shows that pyramidal wet-etch microneedles can penetrate human skin with minimal pain and sensory discomfort, creating transient pathways for potential drug, vaccine and DNA delivery.

Television advertising of pharmacy medicines in the United Kingdom.

In the UK pharmacy is often promoted as the first port of call for minor ailments and the pharmacist's armamentarium of products is increasing as further products are reclassified from prescription only control. Non-prescription medicines in the UK can be advertised directly to the public but the advertisements must comply with the law. Some medicines, namely pharmacy can only be sold from pharmacies by, or under, the supervision of a pharmacist. This report describes the major findings of a postal survey of community pharmacists on the subject of advertising of pharmacy medicines and put them into context by outlining the legal and quasi-legal requirements. Further other studies concerning the advertising of non-prescription medicines are discussed in the context of requests for, and sales of, medicines available without a prescription.

Drug utilization evaluation of nonprescription H2-receptor antagonists and alginate-containing preparations for dyspepsia.

AIMS: To evaluate the use, efficacy and adverse effects of nonprescription H2-receptor antagonists and alginate-containing preparations obtained from community pharmacies. METHODS: Questionnaires were distributed to customers from 39 pharmacies in Scotland and Wales. RESULTS: Of 767 customers recruited, 608 (79.3%) returned an initial questionnaire and 472 (61.5%) customers a second questionnaire. The vast majority of respondents (424, 69.7%) had suffered their symptoms on three or more occasions and 369 (60.7%) had previously tried medicines to relieve their symptoms. Referrals to a doctor were less frequent than recommended in guidelines and few of those who were referred actually saw a doctor. Over a quarter of those returning the second questionnaire claimed to be taking more than one product simultaneously for symptom control. Eight customers who were taking prescribed ulcer-healing drugs obtained H2-receptor antagonists. The majority of respondents (355/472, 75. 2%) obtained some or complete symptom relief using the product obtained and 369/472 (78.2%) were completely satisfied with their product. H2-receptor antagonists were more likely to produce complete relief of symptoms than alginate-containing preparations (P < 0.05). Only 14 respondents (3.0%) reported side-effects from the product used which were mostly gastro-intestinal. CONCLUSIONS: The study demonstrated that drug utilization studies are feasible to carry out in a community pharmacy setting. While the results support published evidence of the efficacy and minimal toxicity of these products, they also highlight the possibility of H2-receptor antagonists being used outwith their licenced indications.

Prescription of antidepressants by general practitioners: recommendations by FHSAs and health boards.

BACKGROUND: In order to cut costs of prescribing by general practitioners family health service authorities (FHSAs) and health boards in the UK have been instructed to improve the quality and cost-effectiveness of prescribing by general practitioners in their area by tailoring advice to individual general practices. AIM: As over 95% of patients suffering from depression are treated by their general practitioner, a study was set up to investigate the effectiveness of the advice given by FHSAs and health boards to general practitioners on treatment of depression and prescription of antidepressant drugs. METHOD: The recommendations on prescription of antidepressants of professional advisors from all 117.FHSAs and health boards in the UK were elicited by telephone. Those who had produced written information for the general practitioners in their area regarding depression and antidepressants prescribing during the study period were asked to send a copy to the researchers. RESULTS: An excellent response rate (100%) was obtained to the telephone survey, and all of the bodies that provided their general practitioners with written information on depression and prescription of antidepressants sent in copies. Most of the documents received were informative and accurate; however, others provided information that was incorrect. CONCLUSION: Bulletins and newsletters from FHSAs and health boards are capable of influencing the prescribing patterns of general practitioners in their area, and must contain accurate and up-to-date information if they are to improve the management of depressed patients in the community.

Preliminary investigation of the efficacy of sublingual verapamil in the management of acute atrial fibrillation and flutter.

The antiarrhythmic properties of sublingual verapamil were investigated in seven patients with acute fast atrial flutter (n = 2) or fibrillation (n = 5). A rapid and significant (P < 0.05) reduction in the ventricular rate was achieved in all seven patients. The ventricular rate at peak plasma verapamil concentration (+/- s.d.) was significantly slower than on admission (101.6 +/- 11.3 and 159 +/- 5.3 beats min-1 respectively, P < 0.01). The ventricular rate remained controlled for over 4 h. Sublingual verapamil was rapidly absorbed with the maximum peak plasma concentration (153.3 +/- 15.5 ng ml-1) being achieved after 1.21 +/- 0.18 h. Side-effects of sublingual verapamil were limited to one report of a bitter taste. The sublingual administration of verapamil may provide an alternative method for the control of acute fast atrial fibrillation and flutter in selected patients.

Pharmacokinetics and pharmacodynamics of verapamil following sublingual and oral administration to healthy volunteers.

1. The pharmacokinetics and pharmacodynamics of verapamil administered via the oral and sublingual routes were compared in a randomised, two-way cross-over study involving six healthy male volunteers. 2. Administered sublingually, a verapamil 40 mg (Securon) crushed tablet produced a significantly higher peak plasma concentration (P less than 0.05), a greater rate of absorption (P less than 0.05), and greater bioavailability (P less than 0.05) when compared with orally administered verapamil 40 mg (Securon). 3. In comparison with oral dosing, PR intervals were significantly (P less than 0.05) prolonged between 30 and 90 min after sublingual verapamil dosing. 4. Correlations between log plasma verapamil concentration and percentage increase in PR interval were greater after sublingual compared with oral dosing in all volunteers.