Unique microneedle arrays prepared from crosslinked polymers, which contain no drug themselves, are described. They rapidly take up skin interstitial fluid upon skin insertion to form continuous, unblockable, hydrogel conduits from attached patch-type drug reservoirs to the dermal microcirculation. Importantly, such microneedles, which can be fabricated in a wide range of patch sizes and microneedle geometries, can be easily sterilized, resist hole closure while in place, and are removed completely intact from the skin. Delivery of macromolecules is no longer limited to what can be loaded into the microneedles themselves and transdermal drug delivery is now controlled by the crosslink density of the hydrogel system rather than the stratum corneum, while electrically modulated delivery is also a unique feature. This technology has the potential to overcome the limitations of conventional microneedle designs and greatly increase the range of the type of drug that is deliverable transdermally, with ensuing benefits for industry, healthcare providers and, ultimately, patients.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Pharmaceutical care programmes delivered by pharmacists are known to improve quality of care for both ambulatory and hospitalized patients with a variety of chronic and acute conditions. • Reduction of HbA1c and normalization of blood pressure are key targets for diabetes care programmes, since they are key to reducing diabetes complications.• Good knowledge about disease, medications, diet and exercise requirements can improve the effectiveness of self-management of diabetes. WHAT THIS STUDY ADDS• In a randomized, controlled clinical trial, a comprehensive pharmaceutical care programme (consisting of patient education and advice on medication adherence, metabolic control and life style) delivered by a clinical pharmacist over a 12-month period, significantly improved glycaemic control and health-related quality of life in Type 2 diabetes patients attending a military hospital outpatient clinic in the United Arab Emirates (UAE).• A significant reduction in HbA1c was important in the reduction of the 10-year coronary heart disease risk scores (by British National Formulary and Framingham methods) seen in patients who received the present care programme.• The outcomes of this study advocate an increased role for clinical pharmacists in the healthcare system in the UAE. AIMSTo examine the influence of a pharmaceutical care programme on disease control and health-related quality of life in Type 2 diabetes patients in the United Arab Emirates. METHODSA total of 240 Type 2 diabetes patients were recruited into a randomized, controlled, prospective clinical trial with a 12-month follow-up. A range of clinical measures, medication adherence and health-related quality of life (Short Form 36) were evaluated at baseline and up to 12 months. Intervention group patients received pharmaceutical care from a clinical pharmacist, whereas control group patients received their usual care from medical and nursing staff. The primary outcome measure was change in HbA 1c. British National Formulary and Framingham scoring methods were used to estimate changes in 10-year coronary heart disease risk scores in all patients. RESULTSA total of 234 patients completed the study. 85.2 mmHg (83.5, 86.8) vs. 76.3 mmHg (74.9, 77.7)] were observed in the intervention group; no significant changes were noted in the control group. The mean Framingham risk prediction score in the intervention group was 10.56% (9.7, 11.4) at baseline; this decreased to 7.7% (6.9, 8.5) (P < 0.001) at 12 months but remained unchanged in the control group. CONCLUSIONSThe pharmaceutical care programme resulted in better glycaemic control and reduced cardiovascular risk scores in Type 2 diabetes patients over a 12-month period.

This paper reviews the recent developments in bioanalysis sample preparation techniques and gives an update on basic principles, theory, applications and possibilities for automation, and a comparative discussion on the advantages and limitation of each technique. Conventional liquid-liquid extraction (LLE), protein precipitation (PP) and solid-phase extraction (SPE) techniques are now been considered as methods of the past. The last decade has witnessed a rapid development of novel sample preparation techniques in bioanalysis. Developments in SPE techniques such as selective sorbents and in the overall approach to SPE, such as hybrid SPE and molecularly imprinted polymer SPE, have been addressed. Considerable literature has been published in the area of solid-phase micro-extraction and its different versions, e.g. stir bar sorptive extraction, and their application in the development of selective and sensitive bioanalytical methods. Techniques such as dispersive solid-phase extraction, disposable pipette extraction and micro-extraction by packed sorbent offer a variety of extraction phases and provide unique advantages to bioanalytical methods. On-line SPE utilizing column-switching techniques is rapidly gaining acceptance in bioanalytical applications. PP sample preparation techniques such as PP filter plates/tubes offer many advantages like removal of phospholipids and proteins in plasma/serum. Newer approaches to conventional LLE techniques (salting-out LLE) are also covered in this review article.

We describe, for the first time, the microbial characterisation of hydrogel-forming polymeric microneedle arrays and the potential for passage of microorganisms into skin following microneedle penetration. Uniquely, we also present insights into the storage stability of these hydroscopic formulations, from physical and microbiological viewpoints, and examine clinical performance and safety in human volunteers. Experiments employing excised porcine skin and radiolabelled microorganisms showed that microorganisms can penetrate skin beyond the stratum corneum following microneedle puncture. Indeed, the numbers of microorganisms crossing the stratum corneum following microneedle puncture was greater than 10 5 cfu in each case. However, no microorganisms crossed the epidermal skin. When using a 21G hypodermic needle, more than 10 4 microorganisms penetrated into the viable tissue and 10 6 cfu of C. albicans and S. epidermidis completely crossed the epidermal skin in 24 h. The hydrogel-forming materials contained no microorganisms following de-moulding and exhibited no microbial growth during storage, while also maintaining their mechanical strength, apart from when stored at relative humidities of 86%. No microbial penetration through the swelling microneedles was detectable, while human volunteer studies confirmed that skin or systemic infection is highly unlikely when polymeric microneedles are used for transdermal drug delivery. Since no pharmacopoeial standards currently exist for microneedle-based products, the exact requirements for a proprietary product based on hydrogel-forming microneedles are at present unclear. However, we are currently working towards a comprehensive specification set for this microneedle system that may inform future developments in this regard.

Although the metabolism and disposition of diclofenac (DF) has been studied extensively, information regarding the plasma levels of its acyl-b-D-glucuronide (DF-AG), a major metabolite, in human subjects is limited. Therefore, DF-AG concentrations were determined in plasma (acidified blood derived) of six healthy volunteers following a single oral DF dose (50 mg). Levels of DF-AG in plasma were high, as reflected by a DF-AG/DF ratio of 0.62 6 0.21 (C max mean 6 S.D.) and 0.84 6 0.21 (area under the concentration-time curve mean 6 S.D.). Both DF and DF-AG were also studied as substrates of different human drug transporters in vitro. DF was identified as a substrate of organic anion transporter (OAT) 2 only (K m = 46.8 mM). In contrast, DF-AG was identified as a substrate of numerous OATs (K m = 8.6, 60.2, 103.9, and 112 mM for OAT2, OAT1, OAT4, and OAT3, respectively), two organic aniontransporting polypeptides (OATP1B1, K m = 34 mM; OATP2B1, K m = 105 mM), breast cancer resistance protein (K m = 152 mM), and two multidrug resistance proteins (MRP2, K m = 145 mM; MRP3, K m = 196 mM). It is concluded that the disposition of DF-AG, once formed, can be mediated by various candidate transporters known to be expressed in the kidney (basolateral, OAT1, OAT2, and OAT3; apical, MRP2, BCRP, and OAT4) and liver (canalicular, MRP2 and BCRP; basolateral, OATP1B1, OATP2B1, OAT2, and MRP3). DF-AG is unstable in plasma and undergoes conversion to parent DF. Therefore, caution is warranted when assessing renal and hepatic transporter-mediated drug-drug interactions with DF and DF-AG.