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Dissolution Profiles (dissolution + profile)
Selected AbstractsDesign of granule structure: Computational methods and experimental realizationAICHE JOURNAL, Issue 11 2006Mansoor A. Ansari Abstract The spatial distribution of solid components and porosity within a composite granule,its microstructure,is an important attribute as it carries information about the processing history of the granule and determines its end-use application properties, particularly the dissolution rate. In this work, the problem of rational design of granule structure is formulated, and two methods for its solution are proposed,stochastic design, which is based on random permutation of points within the structure using the simulated annealing algorithm, and variational design, which is based on direct simulation of granule formation from its constituent primary particles, followed by direct simulation of granule dissolution. The variational design method is demonstrated in a case study of the effect of primary particle size, radial distribution of components, and composition of a two-component granule (active, excipient) on the dissolution profile. Selected granule structures designed computationally were also physically made by fluid-bed granulation, their structure analyzed by X-ray micro-tomography, and dissolution curves measured. It was confirmed that the designed structures are feasible to manufacture and that they meet the required dissolution profiles. © 2006 American Institute of Chemical Engineers AIChE J, 2006 [source] Adduction of amiloride hydrochloride in urea through a modified technique for the dissolution enhancementJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2008Seema Thakral Abstract Amiloride hydrochloride is a potassium-sparing diuretic since it favors sodium excretion and potassium reabsorption. In the present study, urea, a well-known adductor for linear compounds was successfully employed for inclusion of amiloride hydrochloride,a substituted cyclic organic compound through a modified technique. Formation of urea inclusion compounds was confirmed by FTIR, DSC and XRD. The minimum amount of rapidly adductible endocyte (RAE) required for adduction of amiloride hydrochloride in urea was estimated by a modified Zimmerschied calorimetric method. Urea,AH,RAE inclusion compounds containing varying proportions of guests were prepared and their thermal behavior studied by DSC. The inclusion compounds were also found to exhibit high content uniformity and markedly improved dissolution profile as demonstrated by increased dissolution efficiency. Studies reveal the possibility of exploiting co-inclusion of the drug in urea host lattice for the dissolution enhancement. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1191,1201, 2008 [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] 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] 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] 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] 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] In vitro comparative study of three pancreatic enzyme preparations: dissolution profiles, active enzyme release and acid stabilityALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2008A. ALOULOU Summary Background, Various pancreatic enzyme preparations are used for the treatment of pancreatic insufficiency but their bioequivalence is often unknown. Aim, To determine in vitro the pH-dependent release and acid resistance of enzymes from three commercially available pancreatin capsules, two containing enteric-coated (Creon 25000; Eurobiol 25000) and one uncoated (Eurobiol 12500) microspheres. Methods, Dissolution experiments were performed at pH values ranging from 4.0 to 5.8. Lipase, chymotrypsin and amylase activities were measured in the solution as a function of time. Results, Eurobiol 25000 started to release its enzymes significantly at pH 5.0 (t1/2 = 71 min), whereas the enzymes from Creon 25000 were only released at higher pH value (5.4; t1/2 = 49.2 min). Unlike chymotrypsin, lipase and amylase were highly sensitive to acidic conditions at the lowest pH values tested. Both enzymes were also found to be sensitive to proteolytic inactivation at the highest pH values tested. Overall, Eurobiol 25000 released higher amounts of active amylase and lipase than Creon 25000 at the pH values usually found in duodenal contents. The uncoated Eurobiol 12500 preparation was, however, the only one that could immediately release rather high levels of active chymotrypsin and lipase at low pH (4.5). Conclusion, These findings suggest that pH-sensitive enteric-coated pancreatin products containing similar amounts of enzymes might not be bioequivalent depending on the pH of duodenal contents. [source] | |||||||||||||