Drug release rate

Spenlehauer (59) reported that in the case of cisplatin-loaded microspheres, irradiation only changes the processing considerations and does not influence drug release. This observation is in conflict with other literature reports showing increases in drug release rates (60,61). 

The effects of a series of added tertiary amines on the rate of chedn scission of other polyesters, including poly( e-caprolactone-co-lactic acid), has been studied and found to be equally great (65). The mechanism with tertiary amines can only be general base catalysis for the effectiveness of the amines was not related to their pK values or lipophilicities. The acceleration of the hydrolysis of the polyesters was used as a strategy for controlling the drug release rate. 

Chang, R. K., Price, J. C., and Whitworth, C. W., Control of drug release rates through the use of mixtures of poly-caprolactone and cellulose propionate polymers, Pharm. Technol. 10, 24, 26, 29, 32-33, 1986. 

Hendren, R. W., Reel, J. R., and Pitt, G. C., Measurement of drug release rates from sustained delivery devices in vivo. Fort Lauderdale, Florida, Controlled Release Society, Proc. 11th Int. Symp. Control. Rel. Bioact. Materials. 110-111, 1984. 

Intramuscularly administered products typically form a depot in the muscle mass from which the drug is slowly absorbed. The peak drug concentration is usually seen within 1-2 hours. Factors affecting the drug-release rate from an IM depot include the compactness of the depot (the less compact and more diffuse, the faster the release), the rheology of the product, concentration and particle size of drug in the vehicle, nature of the solvent or vehicle, volume of the injection, tonicity of the product, and physical form of the product. 

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. 

Fig. 4. Cyclic change of pH, T, or ionic strength (/) leads to abrupt changes in the drug release rates at certain time intervals in some environmentally responsive polymers.

As shown in Figure 6.21, excellent linearity was obtained, as represented by the high coefficient of correlation obtained for the least square linear regression. Similar results were obtained for the evaluation of autosampler accuracy when other analytes (propyl paraben and rhodamine 110 chloride) were employed in the determinations. Liu et al.9 conducted similar evaluations for the samples employed in the evaluation of the drug release rate profile of OROS with similar results to those discussed above. 

Charrois GJ, Allen TM. Drug release rate influences the pharmacokinetics, biodistribution, therapeutic activity, and toxicity of pegylated liposomal doxorubicin formulations in murine breast cancer. Biochim Biophys Acta 2004 1663(1-2) 167. 

The self-emulsifying behaviour of a binary nonlonlc surfactant vegetable oil mixture has been shown to be dependant on both temperature and surfactant concentration. The quality of the resulting emulsions as assessed by particle size analysis showed that manipulation of these parameters can result In emulsion formulations of controlled droplet size and hence surface area. Such considerations are Important when the partition of lipophilic drugs Into aqueous phases and drug release rates are considered. 

Oral controlled drug-release systems are increasingly used for short half-life drugs to reduce peak blood levels and side-eflfects, to maintain optimum drug concentration and to stimulate patient compliance. In order to maintain a constant blood-level of the drug during an extended period, a constant in vitro drug release rate is desired. The most popular controlled-release system is the matrix tablet (Desai et al., 1965). Te Wierik et al. (1996) reported on... 

The release kinetics of polyelectrolyte-containing controlled release compositions were modeled by Ozturk et al. [331]. According to this analysis the drug release rate depends on intrinsic solubilities as well as pKa values of the drug and polymer. Explicit relationships between release rates and these factors were derived, resulting in successful predictions of experimental data. 

Baert L, Remon JP. Influence of amount of granulation liquid on the drug release rate from pellets made by extrusion spheronization. Int J Pharm 1993 95 135-141. 

Initial process development A preliminary study was established to examine the potential influence of processing parameters on some critical performance attributes of the final product, especially those associated with ultimate drug release rate, and the reproducibility of same. 

Making certain assumptions about formulation issues (both with regard to the substrate being coated, and the coating system being applied), the ultimate influence of the applied coating on drug release rate can be reduced to two key elements, namely ... 

The release profile of ketoprofen from the 2/3 CAP coated core (KET-R CAP tablet) was of zero order (y=0.037x-1.263, r=0.99) and the drug release rate was clearly lower than the original core, as is shown in Fig. 5. However, the technique of preparation of KET-R CAP tablets was somewhat complex, requiring considerable accuracy in the partial coating phase, and not easily applicable on an industrial scale. 

The ketoprofen release profiles from these tablets are shown in Fig. 6. The release curves were linear (r=0.99) and the release rate appeared to decrease with increasing coating amounts. On the basis of the linear inverse relation found between the drug release rate and the coat (Fig. 7), the release rate can be varied with predictable effects by varying the coating amount. In particular the KET-R 15 tablet showed a lower rate of drug release than the 2/3 CAP coated tablet (0.96%/h... 

Since r is constant for a non-biodegradable carrier such as PMMA, the slopes a, P, etc., should reflect changes in the diffusion coefficient D, and therefore differences in porosity, between formulations. The first-order drug release rate constants can be calculated from the slopes of the a and P phases of the release profile. 

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