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Oral Formulations (oral + formulations)
Selected AbstractsPharmacokinetics of a novel transdermal rivastigmine patch for the treatment of Alzheimer's disease: a reviewINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2009A. Kurz Summary Background:, Cholinesterase inhibitors have all been available in oral formulations, but a rivastigmine transdermal patch has now been developed and is approved in many countries worldwide for the treatment of mild-to-moderate Alzheimer's disease (AD) (including the USA, Latin America, Europe and Asia). Objectives:, To review the available pharmacokinetic data that supported the rationale behind the development of the rivastigmine transdermal patch and its clinical effects in dementia therapy. This article will also discuss how the patch may alter the treatment paradigm for patients with AD. Results:, The 9.5 mg/24 h rivastigmine patch was shown to provide comparable exposure to the highest recommended doses of capsules (12 mg/day) with significantly lower maximum plasma concentration (Cmax 8.7 vs. 21.6 ng/ml) and slower absorption rate (tmax 8.1 vs. 1.4 h). In a clinical trial of 1195 AD patients, this translated into similar efficacy with three times fewer reports of nausea and vomiting (7.2% vs. 23.1%, and 6.2% vs. 17.0% respectively). Consequently, more patients in the 9.5 mg/24 h patch group achieved their target therapeutic dose at the end of the study, compared with those in the 12 mg/day capsule group (95.9% vs. 64.4%). Conclusion:, The rivastigmine patch provides continuous drug delivery over 24 h and similar efficacy to the highest recommended dose of oral rivastigmine with improved tolerability. This may allow patients to achieve optimal therapeutic doses and to benefit from a longer duration of treatment. [source] Caregiver preference for rivastigmine patch relative to capsules for treatment of probable Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 5 2007Bengt Winblad Abstract Background Family caregivers comprise a critical component in the care of Alzheimer's disease (AD) patients. Among their many tasks, caregivers are responsible for administering and managing medications. Effective interventions incorporate the needs of both the AD patient and the caregiver, and understanding treatment preferences may maximize intervention effectiveness. Transdermal patches may offer advantages over conventional oral formulations. Methods A 24-week randomized controlled trial compared the rivastigmine patch to the rivastigmine capsule and placebo in patients with probable AD. At baseline and Weeks 8 and 24, the AD Caregiver Preference Questionnaire (ADCPQ) was used to evaluate caregiver expectations, preferences and satisfaction with treatment. Double-dummy treatment blinding ensured that caregiver preference for the patch or capsule was not confounded by perceptions of efficacy or tolerability. Reasons for preference were also elicited. The analytic sample included caregivers who completed the ADCPQ at Weeks 8 and/or 24. Results One thousand and fifty-nine caregivers completed the ADCPQ. More than 70% of caregivers preferred the rivastigmine patch to the capsule. The patch was significantly preferred to the capsule with respect to ease of following the schedule and ease of use. Caregivers indicated greater satisfaction overall, greater satisfaction with administration, and less interference with daily life with the patch versus the capsule (all p,,,0.01). Conclusion Caregivers of AD patients preferred the patch to the capsule for drug delivery. Preference for the rivastigmine patch could potentially lead to improved compliance and improved clinical benefits. Copyright © 2007 John Wiley & Sons, Ltd. [source] Oral quinolones in hospitalized patients: an evaluation of a computerized decision support intervention,JOURNAL OF INTERNAL MEDICINE, Issue 4 2004T. Hulgan Abstract. Objective., To determine whether a computerized decision support system could increase the proportion of oral quinolone antibiotic orders placed for hospitalized patients. Design., Prospective, interrupted time-series analysis. Setting., University hospital in the south-eastern United States. Subjects., Inpatient quinolone orders placed from 1 February 2001 to 31 January 2003. Intervention., A web-based intervention was deployed as part of an existing order entry system at a university hospital on 5 February 2002. Based on an automated query of active medication and diet orders, some users ordering intravenous quinolones were presented with a suggestion to consider choosing an oral formulation. Main outcome measure., The proportion of inpatient quinolone orders placed for oral formulations before and after deployment of the intervention. Results., There were a total of 15 194 quinolone orders during the study period, of which 8962 (59%) were for oral forms. Orders for oral quinolones increased from 4202 (56%) before the intervention to 4760 (62%) after, without a change in total orders. In the time-series analysis, there was an overall 5.6% increase (95% CI 2.8,8.4%; P < 0.001) in weekly oral quinolone orders due to the intervention, with the greatest effect on nonintensive care medical units. Conclusions., A web-based intervention was able to increase oral quinolone orders in hospitalized patients. This is one of the first studies to demonstrate a significant effect of a computerized intervention on dosing route within an antibiotic class. This model could be applied to other antibiotics or other drug classes with good oral bioavailability. [source] Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulationsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2007Héctor R. Guzmán Abstract Biopharmaceutical evaluation of crystalline celecoxib salts in novel solid formulations, which were designed to simultaneously facilitate dissolution and inhibit precipitation in vitro, showed fast and complete absorption in beagle dogs at doses up to 7.5 mg/kg orally. In contrast, 5 mg/kg celecoxib in the form of Celebrex® showed approximately 40% absolute bioavailability in a cross-over experiment. An in vitro,in vivo correlation was observed in dog, and a threshold level of in vitro dissolution needed to maximize in vivo performance was highlighted. Oral bioavailability was limited in the absence of excipient combinations that delayed precipitation of celecoxib free acid as the salt neutralized in the GI fluid. Formulations of crystal forms having high energy (a ,spring'), thus transiently increasing solubility in aqueous solution relative to the free acid, combined with excipients functioning as precipitation inhibitors (,parachutes') were shown to provide both enhanced dissolution and high oral bioavailability. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2686,2702, 2007 [source] Review article: 5-aminosalicylate formulations for the treatment of ulcerative colitis , methods of comparing release rates and delivery of 5-aminosalicylate to the colonic mucosaALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2008G. R. LICHTENSTEIN Summary Background, Many oral 5-aminosalicylic acid (5-ASA) formulations are designed to maximize 5-ASA release in the colon where it acts topically on the colonic mucosa. Delayed-release formulations and azo-prodrugs minimize 5-ASA absorption in the upper gastrointestinal (GI) tract. Aims, To review methods for assessing 5-ASA release and colonic distribution from oral formulations, and the potential use of this information for guiding clinical decisions. Methods, PubMed and recent conference abstracts were searched for articles describing techniques used to assess 5-ASA release from ulcerative colitis (UC) therapies. Results, In-vitro GI models, although unable to simulate more complex aspects of GI physiology, can provide useful data on 5-ASA release kinetics and bioaccessibility. Gamma-scintigraphy is useful for investigating GI disintegration of different formulations, but may not accurately reflect 5-ASA distribution. Plasma pharmacokinetic studies provide data on systemic exposure, but not on colonic distribution or mucosal uptake. Mucosal biopsies provide direct evidence of colonic distribution and may predict clinical efficacy, but must be interpreted cautiously because of considerable inter-subject variability and other confounding factors. Conclusion, While assessment of 5-ASA release is important, limitations of individual measurement techniques mean that randomized clinical studies in UC patients remain the best guide for dosing and treatment regimen decisions. [source] Latest news and product developmentsPRESCRIBER, Issue 2 2008Article first published online: 11 FEB 200 NICE should evaluate all new medicines NICE should determine the cost effectiveness of all new medicines, the Health Select Committee has concluded in its second review of the Institute. The review, prompted by criticisms from patients, health professionals and the pharmaceutical industry, found that NICE is doing ,a vital job in difficult circumstances'. The Committee called for the costs to carers and society to be included in cost effectiveness estimates (this is currently prohibited) and for cost per QALY thresholds to be aligned with NHS affordability. NICE should publish brief appraisals at the time of a product launch , these could be used to negotiate prices. GPs responsible for unlicensed co-proxamol GPs who prescribe co-proxamol are now responsible for the consequences, the MHRA warns. The Agency agrees that the drug may be needed by ,a small group of patients who are likely to find it very difficult to change from co-proxamol or where alternatives appear not to be effective or suitable'. Following the withdrawal of product licences, stock that is currently in the supply chain may be dispensed but no new stock should be released by suppliers. The Drug Tariff price of co-proxamol has now increased from £2.79 to £20.36 per 100 tablets. Vitamin D deficiency on the increase Pregnant and breastfeeding women may need vitamin D supplements, the Department of Health has warned, and GPs are seeing increasing numbers of patients with vitamin D deficiency. Endogenous synthesis may be low in some ethnic groups and dark-skinned people, and north of Birmingham there is no light of the appropriate wavelength for the synthesis of vitamin D during the winter. The Department says free vitamin supplements are available for eligible patients through its Healthy Start Scheme (www.healthystart.nhs.uk) and may also be supplied at low cost by some PCTs. Innovation and good practice recognised Innovative practice and better outcomes for patients have been recognised through awards from the NHS Alliance and Improvement Foundation presented by the Secretary of State for Health, Rt Hon Alan Johnson, at the annual NHS Alliance conference held in Manchester. The Mountwood Surgery in Northwood, Middlesex, won the CHD QOF GP Practice Award sponsored by Schering Plough for their outstanding multidisciplinary approach to tackling CHD. In addition to having a highly organised in-house cardiology team, they have produced an interactive, patient-empowering booklet for CHD. Mountwood Surgery achieved blood pressure targets of 96.79 per cent in their CHD patients. North Tees PCT wins the CHD QOF PCO Award, also sponsored by Schering Plough, for their support and encouragement to GP practices to ,own' CHD care. They provide timely feedback of performance data using funnel plots and regular communication by the CHD LIT and Cardiac Network. Even though North Tees PCT has a high CHD prevalence, 4.2 per cent vs 3.6 per cent nationally, across the 27 practices 85 per cent of patients achieved cholesterol targets and 91 per cent reached the QOF blood pressure target. The St Benedict's Hospice Day Centre Project (for the Sunderland Teaching Primary Care Trust) won the Guy Rotherham Award for its excellent multidisciplinary team improvement of the palliative care provided. This team demonstrated a thorough understanding of the use of quality improvement methods to improve patient care, and carefully measured the individual improvements they made. Through the use of a referral ,decision tree', nonattenders were reduced by 300 per cent and average waiting times halved. The Extended Primary Care (EPC) Gynaecology Service (for the Practice Based Commissioning Consortium South Manchester Hub) was highly commended for its development of an effective and innovative service offering gynaecological treatment managed within a primary care setting, allowing patients improved access closer to home. The Salford Perinatal Mental Health Project was also highly commended for effectively challenging the high levels of maternal suicides. The awards were also supported by Prescriber, the British Cardiac Patients Association and the British Cardiac Society. Anastrozole superior to tamoxifen in long term A new analysis of the ATAC trial (Lancet Oncology 2008;9:45-53) shows that the advantages of the aromatase inhibitor anastrozole (Arimidex) over tamoxifen as adjuvant therapy for breast cancer persist for at least four years after the end of treatment. After primary treatment with surgery, chemotherapy or radiotherapy, postmenopausal women with localised invasive breast cancer were randomised to five years' treatment with anastrozole or tamoxifen. Among 5216 women who were hormone-receptor positive, anastrozole increased disease-free survival by 15 per cent after 100 months. Time to recurrence and distant recurrence were also increased, though overall survival was similar; the absolute difference in time to recurrence was greater at nine years (4.8 per cent) than at five years (2.8 per cent). Joint symptoms and fractures were more frequent with anastrozole during treatment but not thereafter. Use a steroid with a LABA , MHRA reminder The MHRA has reminded clinicians that patients treated with an inhaled long-acting beta-agonist (LABA) should also use an inhaled steroid. In the latest edition of Drug Safety Update (2008;1:No.6), the Agency reviews the implications of the SMART study (Chest 2006;129:15-26), which reported an increased risk of respiratory- and asthma-related deaths among patients using salmeterol (Serevent). This is contradicted by epidemiological data suggesting that asthma-related admissions have declined since LABAs were introduced. Randomised trials also do not support such a risk, probably because inhaled steroids are used more consistently in trial settings. The latest Update notes that product licences for carisoprodol (Carisoma) have been suspended due to concerns about the risk of abuse and psychomotor effects. It also includes a comprehensive summary of drug interactions with statins, a warning that methylene blue should not be prescribed for a patient taking a drug with serotonergic activity, and a reminder that only oral formulations of desmopressin are now licensed for primary nocturnal enuresis. This issue of Update is available at www.mhra.gov.uk. Copyright © 2008 Wiley Interface Ltd [source] Comparative bioavailability of two oral formulations of ranitidineBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2006Francisco J. Flores-Murrieta Abstract The current requirement of the Mexican Authorities to demonstrate the interchangeability of ranitidine formulations is to establish that the dissolution profile of the drug shows similarity. In order to establish if this requirement is adequate, the bioavailability of two formulations that did not meet this similarity were compared. Twenty-five female volunteers received 150 mg ranitidine (Azantac® or Midaven®) under fasting conditions in two separate sessions using a cross-over design. Plasma samples were obtained at selected times for a period of 12 h and stored frozen at ,80°C until analysed. Ranitidine plasma levels were determined and pharmacokinetic parameters were obtained. Values (mean ± SEM) were: Cmax 528.85 ± 25.34 and 563.03 ± 33.25 ng/ml, tmax 2.76 ± 0.19 and 2.79 ± 0.18 h, and AUC12 h 2694.94 ± 99.50 and 2648.51 ± 133.38 ng.h/ml, for Azantac® or Midaven®, respectively. No statistically significant difference was obtained in the parameters evaluated. Moreover, 90% confidence limits were 96.6%,116.2% and 90.7%,105.1% for Cmax and AUC12 h ratios, respectively, indicating that the formulations tested are bioequivalent, despite the dissimilarity in the dissolution profile of the formulations. These results suggest that the comparative dissolution profile is not an adequate test to demonstrate the interchangeability of ranitidine formulations. Copyright © 2005 John Wiley & Sons, Ltd. [source] | ||||||||||