Dissolution profiles

Peh KK, Lim CP, Qwek SS, Khoti KH. Use of artificial networks to predict drug dissolution profiles and evaluation of network performance using similarity profile. Pharm Res 2000 17 1386-98. 

Fig. 5 Dissolution profiles obtained from the solubility determination of two polymorphic forms of the same drug substance. A is the stable form with solubility 31 mg/mL. B is the profile of the metastable form with solubility 46 mg/mL. This solubility (circles) is not achieved in many instances, and precipitation of the stable form occurs at a point beyond the solubility of A, and the trace becomes B. C is the hypothetical profile of the metastable form. 

JW Mauger, SA Howard, K Amin. Dissolution profiles for finely divided drug suspensions. J Pharm Sci 72(2) 190 193, 1983. 

Within the realm of physical reality, and most important in pharmaceutical systems, the unconstrained optimization problem is almost nonexistent. There are always restrictions that the formulator wishes to place or must place on a system, and in pharmaceuticals, many of these restrictions are in competition. For example, it is unreasonable to assume, as just described, that the hardest tablet possible would also have the lowest compression and ejection forces and the fastest disintegration time and dissolution profile. It is sometimes necessary to trade off properties, that is, to sacrifice one characteristic for another. Thus, the primary objective may not be to optimize absolutely (i.e., a maxima or minima), but to realize an overall pre selected or desired result for each characteristic or parameter. Drug products are often developed by teaching an effective compromise between competing characteristics to achieve the best formulation and process within a given set of restrictions. 

Biopharmaceutical issues to be addressed will include a discussion of the pharmaceutical development process as it relates to in vivo and in vitro performance and the general approach taken concerning bioavailability, bioequivalence, and in vitro dissolution profiles. There should be a comparative analysis of relevant studies—objectives, study design, conduct, outcome, and data analyses. The effects of formulation changes (including different strengths of product and... 

VP Shah, JJ Konecny, RL Everett, B McCullough, AC Noorizadeh, JP Skelly. In vitro dissolution profile of water-insoluble drug dosage forms in the presence of surfactants. Pharm Res 6 612-618, 1989. 

D Brooke. Dissolution profile of log-normal powders Exact expression. J Pharm Sci 65 795-798, 1973. 

P. M. Sathe, Y. Tsong, V. Shah. In vitro dissolution profile comparison Statistics and analysis, model dependent approach. Pharm. Res. 1996, 13, 1799-1803. 

The types of intrinsic dissolution profiles obtainable through the loose powder and constant surface area methods are shown in Fig. 19. Oxy-phenbutazone was obtained as the crystalline anhydrate and monohydrate forms, with the monohydrate being the less soluble [129]. The loose powder dissolution profiles consisted of sharp initial increases, which gradually leveled off as the equilibrium solubility was reached. In the absence of supporting information, the solubility difference between the two species cannot be adequately understood until equilibrium solubility conditions are reached. In addition, the shape of the data curves is not amenable to quantitative mathematical manipulation. The advantage of the constant surface area method is evident in that its dissolution profiles are linear with time, and more easily compared. Additional information about the relative surface areas or particle size distributions of the two materials is not required, since these differences were eliminated when the analyte disc was prepared. 

Fig. 19 (a) Loose powder aqueous dissolution profiles for the solubilization at 37°C... 

Fig. 20 Intrinsic aqueous dissolution profiles obtained at 37°C for sulfathiazole, form I ( ), form II O), form III Of). (The data are adapted from Ref. 132.)...

FIGURE 6.39 Dissolution profile of acetaminophen obtained from the Nanostream CL System. 

The theories applied to dissolution have stood the test of time. Basic understanding of these theories and their application are essential for the design and development of sound dissolution methodologies as well as for deriving complementary statistical and mathematical techniques for unbiased dissolution profile comparison (3). 

Gohel MC, Panchal MK. Refinement of lower acceptance value of the similarity Factor F2 in comparison of dissolution profiles. Dissol Technol 2002 9(1). 

Soltero RA, Hoover JM, Jones T, Standish M. Effects of sinker shapes on dissolution profiles. J Pharm Sci 1989 78(l) 35-39. 

The BCS also predicts the possibility of obtaining an in vitro/in vivo correlation. Justification of a biowaiver is based on a combination of the BCS classification of the drug substance and a drug product dissolution profile comparison. In all these instances, an anchor with a bioavailable product is established. Specifically, to obtain a biowaiver for an IR generic product ... 

A biowaiver is applicable for beaded capsules when the lower strength differs only in number of beads of active drug and the dissolution profile is similar in the recommended dissolution test media and conditions. 

A biowaiver is applicable for extended-release tablet formulations, where the lower strength(s) are compo-sitionally similar to the highest strength and uses the same release mechanism and the dissolution profile is similar in pH 1.2, 4.5, and 6.8. 

Among several methods investigated for dissolution profile comparison, the fz factor is the simplest and widely applicable (1). Moore and Flanner (10) proposed a model inde-... 

Dissolution Profile Comparison Model Independent Analysis Similarity Factor... 

Figure 4 Dissolution profile comparison model independent analysis.

Moore JW, Flanner HH. Mathematical comparison of curves with an emphasis on in vitro dissolution profiles. Pharm Tech 1996 206 64-74. 

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