Dissolution rate formulation factors

Numerous studies have probed how novolac microstmcture influences resist hthographic properties. In one example, a series of resists were formulated from novolacs prepared with varying feed ratios ofpara-jmeta-cmso. These researchers found that the dissolution rate decreased, and the resist contrast increased, as thepara-jmeta-cmso feed ratio increased (33). Condensation can only occur at the ortho position ofpara-cmso but can occur at both the ortho- and i ra-positions of meta-cmso. It is beheved that increased steric factors and chain rigidity that accompany increasedpara-cmso content modify the polymer solubihty. 

G. Levy and R. H. Gumtow, Effect of certain tablet formulation factors on dissolution rate of the active ingradient. III. Tablet lubricants, J. Pharm. Sci., 37. 52,1139-1141 (1963). 

White, Effect of certain tablet formulation factors on 38. dissolution rate of the active ingredients. II. Granule... 

A reported application of canonical analysis involved a novel combination of the canonical form of the regression equation with a computer-aided grid search technique to optimize controlled drug release from a pellet system prepared by extrusion and spheronization [28,29]. Formulation factors were used as independent variables, and in vitro dissolution was the main response, or dependent variable. Both a minimum and a maximum drug release rate was predicted and verified by preparation and testing of the predicted formulations. Excellent agreement between the predicted values and the actual values was evident for the four-component pellet system in this study. 

The outcome of dissolution tests on pharmaceutical formulations can be influenced by a nnmber of factors including the nature of the excipients and lubricants, blending method and granulation procedure used. When the solubility of the API is not the limiting factor, the compaction pressure used to produce tablets is inversely proportional to their dissolution rate and, as noted in the previous section, directly proportional to the slope of the NIR spectra for intact tablets. Blanco et have developed various approaches for... 

The effects of various formulation factors on the in vitro release characteristics of spherical polymethylmethacrylate implants were studied. Physical and mathematical models were proposed to describe the in vitro release profiles. The in vitro release data could be described by a biexponential equation of the following type fraction of tobramycin remaining in the implant at time t=Aerai+BQ, where a, and P represent the rate constants for the initial rapid and subsequent slow phases of release. The influence of drug loading, volume of dissolution medium, implant size and type of cement and the incorporation of water-soluble additives on the release profiles and a and P rate constants is described. 

Dissolution of a drug substance is controlled by several physicochemical properties, including solubility, surface area, and wetting properties. For insoluble compounds, dissolution is often the rate-limiting step in the absorption process. Knowledge ofthe dissolution rate of a drug substance is therefore very useful for formulation development. The appropriate dissolution experiments can help to identify factors that contribute to bioavailability problems, and also assist in the selection of the appropriate crystal form and/or salt form. Dissolution tests are also used for other purposes such as quality control and assisting with the determination of bioequivalence (Dressman et al., 1998). 

The degree of ionization under physiologic conditions Product formulation characteristics Disintegration and dissolution rates for solid dosages Drug release characteristics for timed-release preparations Patient factors... 

It is not the aim of this article to evaluate formulation aspects that may influence dissolution of drugs from dosage forms. However, it suffices to mention that dissolution rates of drug substances or drug release from formulated products may be influenced (increased or decreased) by factors such as assay selection, the presence of surfactants, polymorphic modification, and by the use of water-soluble carriers in solid dispersions. 

Use of formulation techniques can improve the bioavailability and/or minimize the toxicity and side effects of drugs. Factors to consider include those that impact on solubility and dissolution rates, chemical and enzymatic stability, and absorption capability. 

---