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Dosage Forms (dosage + form)
Kinds of Dosage Forms Selected AbstractsElectrochemical Evaluation of Nucleoside Analogue Lamivudine in Pharmaceutical Dosage Forms and Human SerumELECTROANALYSIS, Issue 20 2005Burcu Dogan Abstract Lamivudine (LAM) is a synthetic nucleoside analogue with activity against human immunodeficiency virus-type 1 (HIV-1) and Hepatitis B virus (HBV). The aim of this study was to determine LAM levels in serum and pharmaceutical formulations, by means of electrochemical methods using hanging mercury drop electrode (HMDE). On this electrode, LAM undergoes irreversible reduction at the peak potential near Ep,1.26,V (vs. Ag/AgCl/3,M KCl). Reduction LAM signals were measured by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square-wave voltammetry (OSW). DPV and OSW techniques for the determination of LAM in acetate buffer at pH,4.5, which allows quantitation over the 4×10,6 to 1×10,4,M range in supporting electrolyte for both methods, were proposed. The linear response was obtained in acetate buffer in the ranges of 2×10,6 to 2×10,4,M for spiked serum samples at pH,4.5 for both techniques. The repeatability and reproducibility of the methods for all media were determined. The standard addition method was used in serum. Precision and accuracy were also checked in all media. No electroactive interferences from the endogenous substances were found in serum. With respect to side effects of high doses and short half-life of LAM, a fast and simple detection method is described in this study. [source] Voltammetric Determination of ,-Tocopheryl Acetate in Pharmaceutical Dosage FormsELECTROANALYSIS, Issue 11 2004Slawomir Michalkiewicz Abstract A simple and rapid voltammetric method has been developed for the quantitative determination of ,-tocopheryl acetate (,-TOAc) in pharmaceutical preparations. Studies with linear scan (LSV), square-wave (SQWV) and differential pulse voltammetry (DPV) were carried out using platinum microelectrodes. A well-defined, irreversible oxidation wave/peak was obtained at 1.30,V (vs. Ag/AgCl reference electrode.) The use of SQWV or DPV technique provides a precise determination of ,-tocopheryl acetate using the multiple standard addition method. The statistical parameters and the recovery study data clearly indicate good reproducibility and accuracy of the method. Accuracy of the results assessed by recovery trials was found within the 99.3% to 103.5%, and 99.1% to 101.4%, for SQWV and DPV, respectively. The quantification limits for the both voltammetric techniques were found to be 6×10,5,M (SQWV) and 7×10,5,M (DPV). Analysis of the authentic samples containing ,-TOAc showed no interference with common additives and excipients, such as unsaturated fatty acids (co-formulated as glycerine esters) and vitamin A (as retinol or ,-carotene). The method proposed does not require any pretreatment of the pharmaceutical dosage forms. A gas chromatography determination of ,-TOAc in real samples was also performed for comparison. [source] Design and In vitro evaluation of a film-controlled dosage form self-converted from monolithic tablet in gastrointestinal environmentJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2010Tingting Zhang Abstract The purpose of this study is to design an easily manufactured sustained drug delivery system, which can be converted to a film coated system during the dissolution process and then control the drug release according to near zero-order kinetics. Two kinds of pH-sensitive and oppositely charged hydrophilic polymers, chitosan and alginate, were physically mixed as the matrix. Slightly water-soluble drugs such as theophylline, aspirin, and acetaminophen were utilized as model drugs. In vitro drug release and swelling tests were undertaken in simulated gastrointestinal environments. The formation and properties of the film formed during the dissolution process were identified using different techniques. It was demonstrated that formation of the film was based on the interaction of the polymers on tablet surface with the change of system pH. In 0,4,h drug release depended on the intrinsic properties of the polymers, however, characteristics of the film played a leading role in controlling drug release after 4,h. By studying the ratio of relaxation over Fickian diffusion and relationship between tablets swelling and drug release, it was revealed that the film probably modified drug release behavior by limiting polymer erosion. The in vivo behavior of this hydrophilic matrix system will be investigated. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4678,4690, 2010 [source] Biowaiver monographs for immediate release solid oral dosage forms: Diclofenac sodium and diclofenac potassium,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2009B. Chuasuwan Abstract Literature data are reviewed regarding the scientific advisability of allowing a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing either diclofenac potassium and diclofenac sodium. Within the biopharmaceutics classification system (BCS), diclofenac potassium and diclofenac sodium are each BCS class II active pharmaceutical ingredients (APIs). However, a biowaiver can be recommended for IR drug products of each salt form, due to their therapeutic use, therapeutic index, pharmacokinetic properties, potential for excipient interactions, and performance in reported BE/bioavailability (BA) studies, provided: (a) test and comparator contain the same diclofenac salt; (b) the dosage form of the test and comparator is identical; (c) the test product contains only excipients present in diclofenac drug products approved in ICH or associated countries in the same dosage form, for instance as presented in this paper; (d) test drug product and comparator dissolve 85% in 30 min or less in 900 mL buffer pH 6.8, using the paddle apparatus at 75 rpm or the basket apparatus at 100 rpm; and (e) test product and comparator show dissolution profile similarity in pH 1.2, 4.5, and 6.8. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1206,1219, 2009 [source] Design and evaluation of a dry coated drug delivery system with floating,pulsatile releaseJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2008Hao Zou Abstract The objective of this work was to develop and evaluate a floating,pulsatile drug delivery system intended for chronopharmacotherapy. Floating,pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. To overcome limitations of various approaches for imparting buoyancy, we generated the system which consisted of three different parts, a core tablet, containing the active ingredient, an erodible outer shell and a top cover buoyant layer. The dry coated tablet consists in a drug-containing core, coated by a hydrophilic erodible polymer which is responsible for a lag phase in the onset of pulsatile release. The buoyant layer, prepared with Methocel® K4M, Carbopol® 934P and sodium bicarbonate, provides buoyancy to increase the retention of the oral dosage form in the stomach. The effect of the hydrophilic erodible polymer characteristics on the lag time and drug release was investigated. Developed formulations were evaluated for their buoyancy, dissolution and pharmacokinetic, as well gamma-scintigraphically. The results showed that a certain lag time before the drug released generally due to the erosion of the dry coated layer. Floating time was controlled by the quantity and composition of the buoyant layer. Both pharmacokinetic and gamma-scintigraphic data point out the capability of the system of prolonged residence of the tablets in the stomach and releasing drugs after a programmed lag time. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:263,273, 2008 [source] Investigation of human pharmacoscintigraphic behavior of two tablets and a capsule formulation of a high dose, poorly water soluble/highly permeable drug (efavirenz)JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2007J. ZH. Abstract Human pharmacoscintigraphic behavior of two tablets and a capsule formulation of a high dose, poorly water soluble, highly permeable, micronized drug (efavirenz) was investigated. The tablets and capsule, prepared with samarium oxide and neutron activated to produce radioactive samarium-153, were evaluated for their in vivo disintegration and gastrointestinal (GI) transit in healthy subjects under fasted condition. Scintigraphic images were acquired to coincide with blood sampling times to assess the plasma concentration-time profile in relation to in vivo disintegration and GI transit. The mean gastric emptying times were approximately the same for all three formulations. Although in vivo dosage form disintegration was faster for Tablet A as compared to Tablet B and was similar between Tablet A and the capsule, Tablet A showed a slower rate and extent of drug absorption than Tablet B and the capsule. The results of this study eliminated the initial hypothesis that the difference in in vivo performance between the two tablet formulations is due to a different rate of in vivo disintegration and suggest that for this drug the in vivo dissolution rate of the drug from its disintegrated dosage form was a more important factor affecting the rate and extent of drug absorption. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2970,2977, 2007 [source] Microenvironmental pH modulation in solid dosage formsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2007Sherif I. Farag Badawy Abstract There are many reports in the literature referring to the effect of ,microenvironmental pH' on solid dosage form performance, particularly stability and dissolution profiles. Several techniques have been proposed for the measurement of the microenvironmental pH. Those techniques use certain assumptions and approximations and many of them employ a solution calibration curve of a probe to predict hydrogen ion activity in a substantially dry solid. Despite the limitation of the methodology, it is clear from the literature that microenvironmental pH has a significant impact on stability of compounds which demonstrate pH dependent stability in solution. Degradation kinetics of such compounds, and in some cases degradation profile as well, are dependent on the microenvironmental pH of the solid. Modulation of the microenvironmental pH through the use of pH modifiers can hence prove to be a very effective tool in maximizing solid dosage form stability. Judicial selection of the appropriate pH modifier, its concentration and the manufacturing process used to incorporate the pH modifier is necessary to enhance stability. Control of microenvironmental pH to maximize stability can be achieved without the use of pH modifier in some cases if an appropriate counter ion is used to provide an inherently optimal pH for the salt. Microenvironmental pH modulation was also shown to control the dissolution profile of both immediate and controlled release dosage forms of compounds with pH dependent solubility. The pH modifiers have been used in conjunction with high energy or salt forms in immediate release formulations to minimize the precipitation of the less soluble free form during initial dissolution. Additionally, pH modifiers were utilized in controlled release dosage forms of weakly basic drugs which exhibit diminished release in dissolution media with high pH. The incorporation of acidic pH modifiers in the controlled release formulation increases the solubility of the basic drug even as the high pH dissolution medium enters into the dosage form hence increasing drug release rate. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 948,959, 2007 [source] Biowaiver monographs for immediate release solid oral dosage forms: Ibuprofen,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2005H. Potthast Abstract Literature data are reviewed on the properties of ibuprofen related to the biopharmaceutics classification system (BCS). Ibuprofen was assessed to be a BCS class II drug. Differences in composition and/or manufacturing procedures were reported to have an effect on the rate, but not the extent of absorption; such differences are likely to be detectable by comparative in vitro dissolution tests. Also in view of its therapeutic use, its wide therapeutic index and uncomplicated pharmacokinetic properties, a biowaiver for immediate release (IR) ibuprofen solid oral drug products is scientifically justified, provided that the test product contains only those excipients reported in this paper in their usual amounts, the dosage form is rapidly dissolving (85% in 30 min or less) in buffer pH 6.8 and the test product also exhibits similar dissolution profiles to the reference product in buffer pH 1.2, 4.5, and 6.8. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2121-2131, 2005 [source] Physics of amorphous solidsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2004Lori R. Hilden Abstract The physical state of a dosage form, crystalline versus amorphous, is critical in determining its solid-state physical and chemical properties. This minireview describes the physics associated with the preparation and storage of amorphous solids including a review of the common theories of the glass transition and relaxation processes. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:3,12, 2004 [source] Pharmacokinetic/pharmacodynamic studies in drug product developmentJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2002Bernd Meibohm Abstract In the quest of ways for rationalizing and accelerating drug product development, integrated pharmacokinetic/pharmacodynamic (PK/PD) concepts provide a highly promising tool. PK/PD modeling concepts can be applied in all stages of preclinical and clinical drug development, and their benefits are multifold. At the preclinical stage, potential applications might comprise the evaluation of in vivo potency and intrinsic activity, the identification of bio-/surrogate markers, as well as dosage form and regimen selection and optimization. At the clinical stage, analytical PK/PD applications include characterization of the dose,concentration,effect/toxicity relationship, evaluation of food, age and gender effects, drug/drug and drug/disease interactions, tolerance development, and inter- and intraindividual variability in response. Predictive PK/PD applications can also involve extrapolation from preclinical data, simulation of drug responses, as well as clinical trial forecasting. Rigorous implementation of the PK/PD concepts in drug product development provides a rationale, scientifically based framework for efficient decision making regarding the selection of potential drug candidates, for maximum information gain from the performed experiments and studies, and for conducting fewer, more focused clinical trials with improved efficiency and cost effectiveness. Thus, PK/PD concepts are believed to play a pivotal role in streamlining the drug development process of the future. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:18,31, 2002 [source] Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopyJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2009Andrea Heinz Abstract Objectives Solid-state transformations may occur during any stage of pharmaceutical processing and upon storage of a solid dosage form. Early detection and quantification of these transformations during the manufacture of solid dosage forms is important since the physical form of an active pharmaceutical ingredient can significantly influence its processing behaviour, including powder flow and compressibility, and biopharmaceutical properties such as solubility, dissolution rate and bioavailability. Key findings Vibrational spectroscopic techniques such as infrared, near-infrared, Raman and, most recently, terahertz pulsed spectroscopy have become popular for solidstate analysis since they are fast and non-destructive and allow solid-state changes to be probed at the molecular level. In particular, Raman and near-infrared spectroscopy, which require no sample preparation, are now commonly used coupled to fibreoptic probes and are able to characterise solid-state conversions in-line. Traditionally, uni- or bivariate approaches have been used to analyse spectroscopic data sets; however, recently the simultaneous detection of several solid-state forms has been increasingly performed using multivariate approaches where even overlapping spectral bands can be analysed. Summary This review discusses the applications of different vibrational spectroscopic techniques to detect and monitor solid-state transformations possible for crystalline polymorphs, hydrates and amorphous forms of pharmaceutical compounds. In this context, the theoretical basis of solid-state transformations and vibrational spectroscopy and common experimental approaches are described, including recent methods of data analysis. [source] Pharmaceutical applications of mucoadhesion for the non-oral routesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2005Katarina Edsman The adhesion of pharmaceutical formulations to the mucosal tissue offers the possibility of creating an intimate and prolonged contact at the site of administration. This prolonged residence time can result in enhanced absorption and, in combination with a controlled release of the drug, also improved patient compliance by reducing the frequency of administration. During the almost 30 years over which mucoadhesion has been studied, a considerable amount of knowledge has been gained, and much has been learned about the different mechanisms occurring at the formulation-mucus interface and the properties that affect these mechanisms. The in-vivo performance of a dosage form not only depends on the mechanisms occurring at the interface, but also on the properties of the total mucoadhesive complex: the dosage form, the mucosa and the interface between them. A wide variety of methods are used for studying mucoadhesion; some rather similar to the in-vivo situation and some mimicking the interface alone. In this review, the mucus surface, the methods used for the study of mucoadhesion, the different mechanisms involved in mucoadhesion and theories underpinning them have been described. The complexity of mucoadhesion when trying to systemize the subject will also be discussed. The last part of the review describes the buccal, nasal, ocular, vaginal and rectal routes and provides examples of what can be achieved in-vivo when using mucoadhesive formulations. [source] Predictive and correlative techniques for the design, optimisation and manufacture of solid dosage formsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2003Ian J. Hardy ABSTRACT There is much interest in predicting the properties of pharmaceutical dosage forms from the properties of the raw materials they contain. Achieving this with reasonable accuracy would aid the faster development and manufacture of dosage forms. A variety of approaches to prediction or correlation of properties are reviewed. These approaches have variable accuracy, with no single technique yet able to provide an accurate prediction of the overall properties of the dosage form. However, there have been some successes in predicting trends within a formulation series based on the physicochemical and mechanical properties of raw materials, predicting process scale-up through mechanical characterisation of materials and predicting product characteristics by process monitoring. Advances in information technology have increased predictive capability and accuracy by facilitating the analysis of complex multivariate data, mapping formulation characteristics and capturing past knowledge and experience. [source] Comparison of bovine in vivo bioavailability of two sulfamethazine oral boluses exhibiting different in vitro dissolution profilesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2006M. N. MARTINEZ The bolus (or oblet) is a dosage form that can be used for the oral administration of pharmaceutical compounds to ruminating species. Unlike traditional tablets, oral boluses may contain quantities of drug on the order of grams rather than milligrams. Due to its size, it is only recently that USP-like in vitro dissolution methods have been developed for this dosage form. However, whether or not these dissolution tests can predict product in vivo performance has yet to be determined. The importance of this issue is apparent when the U.S. Food and Drug Administration Center for Veterinary Medicine is faced with the decision of whether to require additional in vivo bioequivalence study data to support the approval of changes in product chemistry or manufacturing method. The current study was undertaken to determine whether an in vivo/in vitro correlation can be established for bovine sulfamethazine oral boluses and to acquire insight into the magnitude of changes in in vitro product performance that can occur before corresponding changes are seen in in vivo blood level profiles. Based upon the results of this investigation, it is concluded that marked changes in in vitro sulfamethazine bolus performance can be tolerated before resulting in altered in vivo blood level profiles. However, the data also suggest that rumenal absorption may occur for some compounds. Therefore the degree to which variation in product in vitro dissolution profiles can be tolerated may be compound specific. [source] Pharmacokinetics of nifedipine in TaiwaneseBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 2 2004Shu-Chen Chien Abstract To elucidate the pharmacokinetics of nifedipine in Taiwanese, a retrospective review of nifedipine bioequivalence studies completed in Taiwan in the past 5 years was conducted. A total of 198 healthy male volunteers were given a single dose of a 10 mg Adalat® capsule as a reference drug after overnight fasting. Pharmacokinetic parameters derived from Adalat® administration were calculated by non-compartmental analysis with the WinNonlin program. After oral administration of an immediate-release dosage form of a 10 mg nifedipine capsule to Taiwan residents, a skewed distribution with no clear evidence of bimodality of pharmacokinetic parameters was observed. The mean Cmax was 143.12±53.48 ng/ml, the mean AUC was 293.77±115.62 ng·h/ml, the mean T1/2 was 3.08±1.61 h, and the median value of Tmax was 0.61 h. Compared with other published studies, the Cmax and AUC of nifedipine after 10 mg administration were significantly higher in Taiwanese than in British and American subjects. However, the Cmax and AUC were similar to those of Indian and Mexican subjects. According to the antimode of AUC distribution of 22.5 ng·h/ml/mg proposed by Kleinbloesem, 69.7% of Taiwanese can be categorized as slow metabolizers. Based on the results in this study, the majority of Taiwanese show lower activity of nifedipine metabolism. Copyright © 2004 John Wiley & Sons, Ltd. [source] Pharmacokinetics of lovastatin extended-release dosage form (Lovastatin XL) in healthy volunteersBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2002Michael Lamson Abstract The purpose of this study was to evaluate pharmacokinetics and dose proportionality of lovastatin extended-release dosage form (ER-lovastatin) in the dosage levels of 10, 20 and 40 mg in 9 healthy male subjects. Each subject was randomized to receive a single oral dose of ER-lovastatin either 10, 20 or 40 mg in a three-way crossover design with a washout period of 7 days between the treatments. Subjects were served dinner at approximately 5:30 PM followed by dosing at approximately 10:00 PM in each study period. Serial plasma samples were collected up to 48 h after dosing and assayed for lovastatin and its active metabolite lovastatin acid using an LC/MS/MS method. The plasma concentration,time profiles of lovastatin and its active metabolite lovastatin acid exhibited delayed- and extended-release characteristics at each dose. Mean (±) values for the Cmax of lovastatin were 1.04±0.43, 2.03±0.65 and 4.03±3.02 ng/ml for the 10, 20 and 40 mg dosage, respectively. The corresponding values for the AUC0,48 h of lovastatin were 14.6±7.8, 34.1 ±13.7, and 53.9±35.6 ng h/ml. The same tendency was also found for Cmax and AUC0,48 h values of lovastatin acid. Results from this study demonstrated as the dose of ER-lovastatin increased from 10 to 40 mg, the Cmax and AUC0,48 h values of lovastatin as well as lovastatin acid appeared to increase linearly. Copyright © 2002 John Wiley & Sons, Ltd. [source] Commercial manufacturing scale formulation and analytical characterization of therapeutic recombinant antibodiesDRUG DEVELOPMENT RESEARCH, Issue 3 2004Reed J. Harris Abstract Stable therapeutic antibody dosage forms present production technology challenges, particularly when high-concentration formulations are needed to meet the elevated dose requirements that are generally required for successful antibody therapy. Solid dosage forms, such as lyophilized powders, are generally more stable than liquid formulations. High-concentration drug products can be achieved by reconstitution of the lyophilisate in a smaller volume than its initial (pre-lyophilization) volume, but requires a significant vial overfill. High-concentration liquid formulations are becoming feasible as new techniques and technologies become available. Analytical methods to detect subtle molecular variations have been developed to demonstrate manufacturing consistency. Some molecular heterogeneity is contributed by conserved sites, such as Asn297 glycosylation and the loss of heavy chain C-terminal Lys residues. Characteristics that affect potency, stability, or immunogenicity must be elucidated for each therapeutic antibody. Drug Dev. Res. 61:137,154, 2004. © 2004 Wiley-Liss, Inc. [source] Voltammetric Determination of ,-Tocopheryl Acetate in Pharmaceutical Dosage FormsELECTROANALYSIS, Issue 11 2004Slawomir Michalkiewicz Abstract A simple and rapid voltammetric method has been developed for the quantitative determination of ,-tocopheryl acetate (,-TOAc) in pharmaceutical preparations. Studies with linear scan (LSV), square-wave (SQWV) and differential pulse voltammetry (DPV) were carried out using platinum microelectrodes. A well-defined, irreversible oxidation wave/peak was obtained at 1.30,V (vs. Ag/AgCl reference electrode.) The use of SQWV or DPV technique provides a precise determination of ,-tocopheryl acetate using the multiple standard addition method. The statistical parameters and the recovery study data clearly indicate good reproducibility and accuracy of the method. Accuracy of the results assessed by recovery trials was found within the 99.3% to 103.5%, and 99.1% to 101.4%, for SQWV and DPV, respectively. The quantification limits for the both voltammetric techniques were found to be 6×10,5,M (SQWV) and 7×10,5,M (DPV). Analysis of the authentic samples containing ,-TOAc showed no interference with common additives and excipients, such as unsaturated fatty acids (co-formulated as glycerine esters) and vitamin A (as retinol or ,-carotene). The method proposed does not require any pretreatment of the pharmaceutical dosage forms. A gas chromatography determination of ,-TOAc in real samples was also performed for comparison. [source] Extemporaneous product use in paediatric patients: a systematic reviewINTERNATIONAL JOURNAL OF PHARMACY PRACTICE, Issue 1 2008Ms Jennifer A Giam pharmacist, postgraduate student Objective To identify the relative extent of extemporaneous product use reported in the paediatric population and the implications for pharmacy practice. Method A systematic literature review was undertaken to identify the prevalence of extemporaneous product use in paediatric patients including those studies examining both ,off-label' and unlicensed medicine use from which extemporaneous products were separately identified and compared to licensed drug use. Key findings Twenty studies were identified and evaluated in which extemporaneous products prepared by a pharmacy or licensed manufacturer could be identified. Although prescribing of unlicensed drugs and licensed drugs used ,off-label' occurs more frequently in younger children and for more serious conditions, the use of extemporaneous products is consistent across all age groups and therapeutic areas. Studies using pharmacy dispensing records identified details of extemporaneous products more accurately than studies using prescribing records. Despite efforts to improve the availability of suitable licensed medicine products for children, extemporaneously prepared products are still needed to ensure that optimal drug therapy is available to children in accurate and effective doses and dosage forms. Conclusions Paediatric patients have a continuing need for extemporaneously prepared medicines when suitable dose forms are unavailable from manufacturers. Pharmacists require access to stability, compatibility and formulation information, as well as appropriate training to ensure patients are supplied with high-quality, safe and effective preparations. [source] Antimalarial drug quality in AfricaJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2007A. A. Amin PhD Abstract Background and objective: There are several reports of sub-standard and counterfeit antimalarial drugs circulating in the markets of developing countries; we aimed to review the literature for the African continent. Methods: A search was conducted in PubMed in English using the medical subject headings (MeSH) terms: ,Antimalarials/analysis'[MeSH] OR ,Antimalarials/standards'[MeSH] AND ,Africa'[MeSH]' to include articles published up to and including 26 February 2007. Data were augmented with reports on the quality of antimalarial drugs in Africa obtained from colleagues in the World Health Organization. We summarized the data under the following themes: content and dissolution; relative bioavailability of antimalarial products; antimalarial stability and shelf life; general tests on pharmaceutical dosage forms; and the presence of degradation or unidentifiable impurities in formulations. Results and discussion: The search yielded 21 relevant peer-reviewed articles and three reports on the quality of antimalarial drugs in Africa. The literature was varied in the quality and breadth of data presented, with most bioavailability studies poorly designed and executed. The review highlights the common finding in drug quality studies that (i) most antimalarial products pass the basic tests for pharmaceutical dosage forms, such as the uniformity of weight for tablets, (ii) most antimalarial drugs pass the content test and (iii) in vitro product dissolution is the main problem area where most drugs fail to meet required pharmacopoeial specifications, especially with regard to sulfadoxine,pyrimethamine products. In addition, there are worryingly high quality failure rates for artemisinin monotherapies such as dihydroartemisinin (DHA); for instance all five DHA sampled products in one study in Nairobi, Kenya, were reported to have failed the requisite tests. Conclusions: There is an urgent need to strengthen pharmaceutical management systems such as post-marketing surveillance and the broader health systems in Africa to ensure populations in the continent have access to antimalarial drugs that are safe, of the highest quality standards and that retain their integrity throughout the distribution chain through adequate enforcement of existing legislation and enactment of new ones if necessary, and provision of the necessary resources for drug quality assurance. [source] Controlled drug delivery: therapeutic and pharmacological aspectsJOURNAL OF INTERNAL MEDICINE, Issue 5 2000J. Urquhart Abstract. Urquhart J (Department of Epidemiology, Pharmaco-epidemiology Group, Maastricht University, Maastricht, the Netherlands). Controlled drug delivery: therapeutic and pharmacological aspects (Internal Medicine in the 21st Century). J Intern Med 2000; 248: 357,376. Concerted work to develop human pharmaceuticals based on rate-controlled drug delivery systems began in 1970. Today there are over three dozen such products, plus a few for veterinary use. In addition, osmotic minipumps have been extensively used since 1978, resulting in over 6000 publications in the pharmacological, endocrinological and physiological literature. Rate-controlled delivery provides for drug entry into the bloodstream continuously at either a constant or a modulated rate. By this means, one avoids the usual peak and trough pattern of drug concentrations in plasma, with its echoing peak and trough pattern of drug actions, during the interval between successive doses. In contrast to the happenstance release kinetics of rapid-release dosage forms, rate-controlled delivery systems can be designed to provide specific temporal patterns of drug concentration in plasma, for the purpose of optimizing the selectivity of drug action, the interval between successive administerings of drug and the likelihood that the next administering will occur at the proper time. [source] ESI+ MS/MS confirmation of canine ivermectin toxicity,JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2009A. F. Lehner Abstract Ivermectin is a semisynthetic macrocyclic lactone anthelmintic of the avermectin family derived from Streptomyces fermentation products. Avermectins are used as antiparasitic agents in domestic animals; although considered relatively safe, one must consider animal species, breed, weight, and age in dosage determinations. In January 2006, two canines were presented to the UK Livestock Disease Diagnostic Center after dying from suspected ivermectin overdoses [30,50 mg/kg body weight]. To confirm this clinical diagnosis we developed a rapid, sensitive semiquantitative ElectroSpray Ionization,Mass Spectrometry (ESI/MS) method for ivermectin in canine tissue samples. Pharmaceutical ivermectin contains two ivermectins differing by a single methyl group, and each compound forms interpretation-confounding adducts with tissue Na+ and K+ ions. We now report that ivermectin administration was clearly confirmed by comparison with standard and dosage forms of ivermectin, and simple proportionalities based on mass spectral intensity of respective molecular ions allowed semiquantitative estimates of injection site tissue concentrations of 20 and 40 µg/g tissue (wet weight) in these animals, consistent with the history of ivermectin administration and the clinical signs observed. There is a distinct need for both rapid detection and confirmation of toxic exposures in veterinary diagnostics, whether for interpretation of clinical cases antemortem or for forensic reasons postmortem. It is vital that interpreters of analytical results have appropriate guidance in the scientific literature and elsewhere so as to enable clear-cut answers. The method presented here is suitable for routine diagnostic work in that it allows rapid extraction of ivermectin from tissue samples, avoids the need for high-performance liquid chromatography and allows ready interpretation of the multiple ivermectin species seen by ESI+ MS/MS in samples originating from veterinary dosage forms. Copyright © 2008 John Wiley & Sons, Ltd. [source] Quality specifications for peptide drugs: a regulatory-pharmaceutical approachJOURNAL OF PEPTIDE SCIENCE, Issue 11 2009Valentijn Vergote Abstract Peptide drugs, as all types of pharmaceuticals, require adequate specifications (i.e. quality attributes, procedures and acceptance criteria) as part of their quality assurance to ensure the safety and efficacy of drug substances (i.e. active pharmaceutical ingredients) and drug products (i.e. finished pharmaceutical dosage forms). Compendial monographs are updated regularly to keep up with the most recent advances in peptide synthesis (e.g. reduced by-products) and analytical technology. Nevertheless, currently applied pharmacopoeial peptide specifications are barely harmonized yet (e.g. large differences between the European Pharmacopoeia and the United States Pharmacopeia), increasing the manufacturers' burden of performing analytical procedures in different ways, using different acceptance criteria. Additionally, the peptide monographs are not always consistent within a single pharmacopoeia. In this review, we highlight the main differences and similarities in compendial peptide specifications (including identification, purity and assay). Based on comparison, and together with additional information from peptide drug substance manufacturers and public evaluation reports on registration files of non-pharmacopoeial peptide drugs, a consistent monograph structure is proposed. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [source] Biowaiver monographs for immediate release solid oral dosage forms: Doxycycline hyclate,,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2010E. Jantratid Abstract Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing doxycycline hyclate are reviewed. According to the Biopharmaceutics Classification System (BCS), doxycycline hyclate can be assigned to BCS Class I. No problems with BE of IR doxycycline formulations containing different excipients and produced by different manufacturing methods have been reported and hence the risk of bioinequivalence caused by these factors appears to be low. Doxycycline has a wide therapeutic index. Further, BCS-based dissolution methods have been shown to be capable of identifying formulations which may dissolve too slowly to generate therapeutic levels. It is concluded that a biowaiver is appropriate for IR solid oral dosage forms containing doxycycline hyclate as the single Active Pharmaceutical Ingredient (API) provided that (a) the test product contains only excipients present in doxycycline hyclate IR solid oral drug products approved in the International Conference on Harmonization (ICH) or associated countries; and (b) the comparator and the test products comply with the BCS criteria for "very rapidly dissolving" or, alternatively, when similarity of the dissolution profiles can be demonstrated and the two products are "rapidly dissolving.". © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1639,1653, 2010 [source] Anomalous properties of spray dried solid dispersionsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2009Hisham Al-Obaidi Abstract The use of solid dispersions for oral dosage forms can increase the dissolution rate of poorly soluble drugs. Spray drying is one process that can be used to prepare solid dispersions. Spray dried solid dispersions of griseofulvin, poly[N -(2-hydroxypropyl)methacrylate] (PHPMA) and polyvinylpyrrolidone (PVP) were prepared from acetone and water. When methanol was substituted for water, the morphology, stability and dissolution properties of the solid dispersion changed dramatically. The glass transition temperature for the ternary solid dispersion (GF, PHPMA, and PVP) shifted from 83°C (acetone/water) to 103°C for the acetone/methanol system. These differences in the dispersions are thought to derive from conformational variations of the polymers in solution prior to spray drying. Both PHPMA and PVP formed globules in solution of a size range between 16 and 33 nm. The effect of drug and polymer concentration in solution (before spray drying) on the properties of the solid dispersion was studied. It was found that solid dispersions that were prepared using lower concentrations of drug and polymers in solutions resulted in the formation of particles that display a lower relaxation rate. This result supports the hypothesis that the polymer conformation may significantly change the properties of the solid dispersion. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4724,4737, 2009 [source] Monitoring the film coating unit operation and predicting drug dissolution using terahertz pulsed imagingJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2009Louise Ho Abstract Understanding the coating unit operation is imperative to improve product quality and reduce output risks for coated solid dosage forms. Three batches of sustained-release tablets coated with the same process parameters (pan speed, spray rate, etc.) were subjected to terahertz pulsed imaging (TPI) analysis followed by dissolution testing. Mean dissolution times (MDT) from conventional dissolution testing were correlated with terahertz waveforms, which yielded a multivariate, partial least squares regression (PLS) model with an R2 of 0.92 for the calibration set and 0.91 for the validation set. This two-component, PLS model was built from batch I that was coated in the same environmental conditions (air temperature, humidity, etc.) to that of batch II but at different environmental conditions from batch III. The MDTs of batch II was predicted in a nondestructive manner with the developed PLS model and the accuracy of the predicted values were subsequently validated with conventional dissolution testing and found to be in good agreement. The terahertz PLS model was also shown to be sensitive to changes in the coating conditions, successfully identifying the larger coating variability in batch III. In this study, we demonstrated that TPI in conjunction with PLS analysis could be employed to assist with film coating process understanding and provide predictions on drug dissolution. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4866,4876, 2009 [source] Assessment of diffuse transmission mode in near-infrared quantification,part I: The press effect on low-dose pharmaceutical tabletsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2009M. Saeed Abstract Quantitative applications for pharmaceutical solid dosage forms using near-infrared (NIR) spectroscopy are central to process analytical technology (PAT) manufacturing designs. A series of studies were conducted to evaluate the use of NIR transmission mode under various pharmaceutical settings. The spectral variability in relation to tablet physical parameters were investigated using placebo tablets with different thickness and porosity steps and both variables showed an exponential relationship with the detected transmittance signal drop. The drug content of 2.5% m/m folic acid tablets produced under extremely different compaction conditions was predicted and found to agree with UV assay results after inclusion of extreme physical outliers to the training sets. NIR transmission was also shown to traverse a wide section of the tablet by comparing relative blocking intensities from different regions of the tablet surface and >90% of the signal was detected through a central area of 7 mm diameters of the tablet surface. NIR Quantification of both film thickness and active ingredient for film-coated tablets are examined in part II of this study. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4877,4886, 2009 [source] Current status of amorphous formulation and other special dosage forms as formulations for early clinical phasesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2009Kohsaku Kawakami Abstract Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2875,2885, 2009 [source] Biowaiver monographs for immediate release solid oral dosage forms: Quinidine sulfate,,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2009S. Grube Abstract Literature data are reviewed relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of new multisource and reformulated immediate release (IR) solid oral dosage forms containing quinidine sulfate. Quinidine sulfate's solubility and permeability, its therapeutic use and index, pharmacokinetics, excipient interactions and reported BE/bioavailability (BA) problems were taken into consideration. The available data are not fully conclusive, but do suggest that quinidine sulfate is highly soluble and moderately to highly permeable and would likely be assigned to BCS Class I (or at worst BCS III). In view of the inconclusiveness of the data and, more important, quinidine's narrow therapeutic window and critical indication, a biowaiver based approval of quinidine containing dosage forms cannot be recommended for either new multisource drug products or for major postapproval changes (variations) to existing drug products. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2238,2251, 2009 [source] Development of clinical dosage forms for a poorly water-soluble drug II: Formulation and characterization of a novel solid microemulsion preconcentrate system for oral delivery of a poorly water-soluble drugJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2009Ping Li Abstract The solution of a poorly water-soluble drug in a liquid lipid,surfactant mixture, which served as a microemulsion preconcentrate, was converted into a solid form by incorporating it in a solid polyethylene glycol (PEG) matrix. The solid microemulsion preconcentrates thus formed consisted of Capmul PG8 (propylene glycol monocaprylate) as oil, Cremophor EL (polyoxyl 35 castor oil) as surfactant, and hydrophilic polymer PEG 3350 as solid matrix. The drug (aqueous solubility: 0.17 µg/mL at pH 1,8 and 25°C) was dissolved in a melt of the mixture at 65,70°C and then the hot solution was filled into hard gelatin capsules; the liquid gradually solidified upon cooling below 55°C. The solid system was characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), confocal Raman microscopy (CRM), and the dispersion testing in water. It was confirmed that a solid microemulsion preconcentrate is a two-phase system, where clusters of crystalline PEG 3350 formed the solid structure (m.p. 55,60°C) and the liquid microemulsion preconcentrate dispersed in between PEG 3350 crystals as a separate phase. The drug remained dissolved in the liquid phase. In vitro release testing showed that the preconcentrate dispersed readily in water forming a microemulsion with the drug dissolved in the oil particles (<150 nm) and the presence of PEG 3350 did not interfere with the process of self-microemulsification. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1750,1764, 2009 [source] | |||||||||||||