Hydrophilic matrices

Influence of drug solubility in the formulation of hydrophilic matrices... 

INFLUENCE OF DRUG SOLUBILITY IN THE FORMULATION OF HYDROPHILIC MATRICES 15... 

Formulation of hydrophilic matrices with a release time longer than 8 h is difficult with drugs and C, owing to the high solubility of the substances contrary to slightly soluble drugs (e.g. drug... 

Hardness had no marked effect on release characteristics except for wax matrices. With hydrophilic matrices, for methylcellulose, increased matrix material concentration did not affect the release profile, but for carbomer, as the concentration increased, a significant decrease in released amount was obtained. 

Goodness-of-fit analysis applied to release data showed that the release mechanism was described by the Higuchi diffusion-controlled model. Confirmation of the diffusion process is provided by the logarithmic form of an empirical equation (Mt/ M=ktn) given by Peppas. Positive deviations from the Higuchi equation might be due to air entrapped in the matrix and for hydrophilic matrices due to the erosion of the gel layer. Analysis of in vitro release indicated that the most suitable matrices were methylcellulose and glycerol palmitostearate. 

The aim of this investigation was to create a sustained release dosage form to provide a constant blood level pattern for up to 12 h after oral administration of ketoprofen. Three different techniques for delaying drug release from hydrophilic matrices of hydroxyproplmethylcellulosc were evaluated. 

Varying amounts of Precirol in Precirol drug ratios of 1 3 (KET-R A), 1 2 (KET-R B) and 1 1 (KET-R C) were added to the above formulation for hydrophilic matrices. The properties of these tablets are shown in Table 1 (average of 20 measurements). 

The use of cellulose ethers in producing matrix-type sustained release tablets is well documented [7]. Hydrophilic matrices of ketoprofen with hydroxypropylmethylcellulose (KET-R)... 

Of the techniques examined for delaying drug release from hydrophilic matrices of HPMC, only Precirol incorporation proved ineffective. 

Figure 3 Release from hydrophilic matrices with Tramal /Contramal /Adolonta long of Gruenenthal as an example.

Figure 4.3 Released amount Qt versus time t plots. Three characteristic drug release profiles from hydrophilic matrices, diffusional, ero-sional, and analamous.

Solubility enhancement. Developing CR formulations of poorly soluble drugs could be challenging at time, yet there are some benefits. For moderately insoluble compounds, the corresponding release of drug molecules was found to be similar to that of HPMC.47 As discussed earlier, it can be straightforward to develop hydrophilic matrices for such molecules to achieve zero-order release because polymer release now can be calculated accurately based on the spaghetti model. 

Ju, T., Nixon, P., and Patel, M. Drug release from hydrophilic matrices I. New scaling laws for predicting polymer and drug release based on the polymer disentanglement concentration and the diffusion layer. J. Pharm. Sci. 84 1455—1463, 1995. 

Conte, U., Maggi, L., Colombo, P., and Manna, A. Multilayered hydrophilic matrices as constant release devices (Geomatrix systems). J. Contr. Rel. 26 39-47, 1993. 

Lapidus, H. and Lordi, N., Drug release from compressed hydrophilic matrices, Journal of Pharmaceutical Sciences, Vol. 57, No. 8, 1968, pp. 1292-1301. 

Siepmann, J. and Peppas, N., Hydrophilic matrices for controlled drug delivery An improved mathematical model to predict the resulting drug release kinetics (the sequential layer model), Pharmaceutical Research, Vol. 17, No. 10, 2000, pp. 1290-1298. 

The factors influencing the release of drugs from hydrophilic matrices include viscosity of the polymer, ratio of the polymer to drug, mixtures of polymers, compression pressure, thickness of the tablet, particle size, pH of the matrix, entrapped air in the tablet, solubility of the drug, the presence of excipients or additives, and the mode of incorporation of these substances. 

Leuenberger et al. introduced percolation theory in the pharmaceutical field in 1987 to explain the mechanical properties of compacts and the mechanisms of the formation of a tablet [36,37]. Knowledge of the percolation thresholds of a system results in a clear improvement of the design of controlled-release dosage forms such as inert or hydrophilic matrices. 

Recently percolation theory is starting to be applied to the study of hydrophilic matrix systems. Figure 41 shows an example of the changes observed in several release parameters employed to estimate the critical point and the related percolation threshold in hydrophilic matrices prepared using KC1 as the model drug [73],... 

Miranda et al. demonstrated experimentally the influence of the particle size of the components on the percolation threshold in hydrophilic matrices as well as the importance of the initial porosity in the formation of the gel layer (sample-spanning cluster of excipient) [74],... 

The principles of the percolation theory were applied to design controlled-release matrix tablets containing acyclovir in order to estimate the percolation threshold of the excipient in acyclovir matrix tablets and to characterize the release behavior of these hydrophilic matrices in order to rationalize the design of these controlled-release systems. 

TABLE 24 Composition of Hydrophilic Matrices Prepared with Acyclovir/HPMC K4M (150-200 pm) and Percent HPMC pins Initial Porosity... 

Figure 42 shows the release profiles obtained from hydrophilic matrices formulated with acyclovir and HPMC K4M 150-200 pm. 

TABLE 25 Aspect Ratios and Exponent Values (m) for Hydrophilic Matrices Studied... 

In hydrophilic matrices the drug threshold is less evident than the excipient threshold, which is responsible for the release control [73], In order to estimate the percolation threshold of HPMC K4M, different kinetic parameters were studied Higuchi rate constant, normalized Higuchi rate constant, and relaxation rate constant. The evolution of these release parameters has been studied as a function of the sum of the excipient volumetric percentage plus initial porosity. Recent studies of our research group have found the existence of a sample-spanning cluster of excipient plus pores in the hydrophilic matrix before the matrix is placed in contact with the liquid, clearly influences the release kinetics of the drug [73]. 

Second, the excipient percolation threshold in hydrophilic matrices represents the border between a fast release of the drug (below the threshold) and a drug release controlled by the formation of a coherent gel layer (above the excipient percolation threshold). Therefore, knowledge of this threshold will allow us to avoid the preparation of a number of unnecessary lots during the development of a pharmaceutical formulation, resulting in a reduction of the time to market. 

Miranda, A., Millan, M., and Caraballo, I. (2006), Study of the critical points in Loben-zarit disodium hydrophilic matrices for controlled drug delivery, Chem. Pharm. Bull. 54,598-602. 

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