Dissolution behavior

The most commonly used polymers are cellulose acetate phthalate [9004-38-0] (CAP), poly(vinyl acetate phthalate) [34481-48-6] (PVAP), hydroxypropylmethyl-ceUulosephthalate [71138-97-1] (HPMCP), and polymethacrylates (111) (see Cellulose esters). Acrylate copolymers are also available (112). Eigure 11 shows the dissolution behavior of some commercially available enteric materials. Some manufacturers supply grades designed to dissolve at specific pH values with increments as small as 0.5 pH unit (113). 

G Levy, JA Procknal. Unusual dissolution behavior due to film formation. J Pharm Sci 51 294, 1962. 

The rate at which selected liquids penetrate into tablets can be used to study their pore structure. A knowledge of the rate of liquid penetration should also provide information on the disintegration/dissolution behavior of a tablet on administration. Such investigations are capable of forming a valuable link between physico-mechanical characteristics and in vivo performance. 

PT Shah, WE Moore. Dissolution behavior of commercial tablets extemporaneously converted to capsules. J Pharm Sci 59 1034-1036, 1970. 

Measurements of the dissolution behavior of polymorphic forms of relatively insoluble drugs are a convenient way of measuring thermodynamic parameters which, in turn, provide a rational approach to selection of the more energetic polymorphic forms of these drugs for absorption. Large differences in free energy... 

Tables 3 and 4 list thermodynamic values calculated for polymorphs of chloramphenicol palmitate and mefenamic acid, respectively. Absorption studies of chloramphenicol palmitate in humans show that suspensions containing polymorph B of chloramphenicol palmitate gave blood levels approximately 10 times higher than those produced by suspensions of polymorph A [49], This may be due to the significant (-774 cal/mol) free energy difference between the polymorphs resulting in a substantial difference in their solubility and dissolution behavior. This theory is supported by the almost identical blood levels due to polymorphs I and n of mefenamic acid, which have a small free energy difference (-231 cal/mol) and similar solubility and dissolution behavior (Table 4).

A Aguiar, JE Zelmer. Dissolution behavior of polymorphs of chloramphenicol pal-mitate and mefenamic acid. J Pharm Sci 58(8) 983-987, 1969. 

E Shefter, T Higuchi. Dissolution behavior of crystalline solvated and nonsolvated forms of some pharmaceuticals. J Pharm Sci 52 781-791, 1963. 

Mechanisms of dissolution kinetics of crystals have been intensively studied in the pharmaceutical domain, because the rate of dissolution affects the bioavailability of drug crystals. Many efforts have been made to describe the crystal dissolution behavior. A variety of empirical or semi-empirical models have been used to describe drug dissolution or release from formulations [1-6]. Noyes and Whitney published the first quantitative study of the dissolution process in 1897 [7]. They found that the dissolution process is diffusion controlled and involves no chemical reaction. The Noyes-Whitney equation simply states that the dissolution rate is directly proportional to the difference between the solubility and the solution concentration ... 

Film dissolution behavior Cross-link density gel nature chemical vs. physical. 

In recent years, with growing concern about the relative bioavailabilities of different samples of the same drug substance, polymorphism has become of prime interest. Miyazaki and co-workers (23) have reported the existence of two crystalline forms of CTC-HCl. The X-ray powder diffraction patterns, IR spectra, dissolution behaviors, and hygroscopicities that they reported were distinctly different and there were discrepancies in the bioavailabilities. 

Despite the small amount of acid generated in these experiments, the film dissolution behavior following postbake is dramatically affected. Acid content exceeding 5 x 10 6 mmol per 2 inch wafer is sufficient to change the solubility characteristics of the resist such that exposed resist film is no longer soluble in nonpolar developer solvent. 

Effect of Oxide Mineralogy on Reductive Dissolution. Oxide/hydrox-ide surface structures and the coordinative environment of metal centers may change substantially throughout the course of a reductive dissolution reaction. Nonstoichiometric and mixed oxidation state surfaces produced during surface redox reactions may exhibit dissolution behavior that is quite different from that observed with more uniform oxide and hydroxide minerals. 

The dissolution fluid flow characteristics should consist of a predictable pattern that is free of irregularities or variable turbulence. Observations of the product dissolution behavior are critical when choosing a dissolution apparatus. If there are aberrant or highly variable data that can be attributed to the apparatus, then it may be unsuitable for that product. 

Lobenberg R, Kraemer J, Shah VP, Amidon GL, Dressman JB. Dissolution testing as a prognostic tool for oral drug absorption dissolution behavior of glibenclamides. Pharm Res 2000 17 439-444. 

Figure 3 Full-change method to determine whether poor disintegration at pH 1.2 would adversely affect subsequent dissolution behavior at pH 6.8.

Figure 12 Simulation output for the slow formulation whose dissolution behavior is shown in Figure 3. Pharmacokinetic parameters F= 1, ka = 1000 hr-1, kw = 0.17 hr-1, V = 114L,/c0i = 1, tcol = 9 hr, ahs 96 hr. Dosing parameters dose = 10 mg, i = 24hr. IVIVC equation 4th order polynomial shown in Figure 11. Double Weibull (drug release) parameters Finf=102%, fi = 0.349, MDTa = 6.85 hr, 61 = 0.783, MDT2=18.7hr, and b2 = 2.11 (Table 2).

Independent of existing intra-lot variability, a sample size of six dosage units is generally recognized to suffice the needs of quality control (QC). In very early development less than six specimens may be used to create data, but as soon as possible tests should be run with at least n = 6. It is advisable to create statistically valid and sound data for manufacturing prototypes even at very early phases of development, in order to be able to identify formulations/batches with unwanted dissolution behavior. In the early phases of a drug product s development, formulations may not be of acceptable stability. This means that stability phenomena may mask... 

All electrochemical etch stops of silicon are based on the dissolution behavior discussed above and a method to have different parts of the electrode interface under different potentials. 

Sun et al. [382] have studied the dissolution behavior of gold and silver from Au—Ag alloys in aerated cyanide solutions using rotating disc electrodes. 

Shulman, M., M. Jacobson, R. Charlson, R. Synovec, and T. Young, Dissolution Behavior and Surface Tension Effects of Organic Compounds in Nucleating Cloud Droplets, Geophys. Res. Lett., 23, 277-280 (1996). 

Adachi, T., Ohnuki, M. et al. 1990. Dissolution study of spent PWR fuel Dissolution behavior and chemical properties of insoluble residues. Journal of Nuclear Materials, 174, 60-71. 

Performance Cohesive and adhesive properties, surface free energy, and water uptake behavior affect disintegration and dissolution behavior... 

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