Relationship between Surface Properties and In Vitro Drug Release from a Compressed Matrix Containing an Amphiphilic Polymer Material

Abstract

The performance of compressed tablet drug delivery systems made using polymeric materials depend on multiple factors, such as surface properties like contact angle, surface free energy and water absorption rate, besides the release mechanisms driven by the kind of polymer used. Hence, it should be possible to establish a relationship between the surface properties and the drug release kinetics. Compressed tablets with different proportions of poly(maleic acid-alt-octadecene) potassium salt (0%, 10%, 20%, 30% and 40%) were prepared. Blends of a model drug (ampicillin trihydrate) and the polymer material were analyzed by DSC. The surface properties of the tablets were determined by the sessile drop method, while the surface energy was determined using the semi-empirical Young-Dupre, Neumann and OWRK models. The release profiles were determined simulating in vitro conditions (buffer solutions pH 1.2 and pH 7.4 with ionic strength of 1.5 M at 37 °C (310.15 K)). A kinetic analysis of the dissolution profiles using different models (zero order, first order, Higuchi and Korsmeyer-Peppas) was realized. The results showed a significant effect of the proportion of polymer in both the surface properties of the tablets and the dissolution release, indicating a relationship between the kinetic and thermodynamic properties.

Relationship between Surface Properties and In Vitro Drug Release from Compressed Matrix Containing Polymeric Materials with Different Hydrophobicity Degrees

“…Furthermore, the data of disintegration time are also very interesting, for the PAM-4Na polymer, which is a hydrophilic low molecular weight material; the matrix disintegration is almost immediate and occurs in a similar way as a conventional release tablet; on the other hand, the PAM-18Na polymer is amphiphilic in nature and shows an increasing disintegration time, due to the high cohesiveness degree of the tablet. This result is quite similar to that obtained in a previous study, where a similar amphiphilic material was used, but with a potassium counter ion [ 27 ]. In contrast, the hydrophobic polymer PAM-18 showed a rapid disintegration attributed to the low hardness of the tablet; while the reference polymer HPMC showed higher values of disintegration time because such a matrix might swell in aqueous media forming gel-like structures that are difficult to disintegrate [ 21 ].…”

“…On the other hand, for tablets containing PAM-4Na, it is observed that increasing the amount of polymer leads to a slight and gradual increase of θ c . In the case when the tablets contain PAM-18Na, the results are very close to those previously found with a similar polymer, such as PAM-18K [ 27 ], where at polymeric proportions of 10% and 20%, θ c is much lower compared to the value shown by the surfaces of the ampicillin tablets, whereas at polymer proportions of 30% and 40%, θ c values are greater and very close to 90°, suggesting a transition from a hydrophilic to a hydrophobic surface.…”

“…For ampicillin trihydrate, there are a variety of polar functional groups that allow it to interact attractively with the ultrapure water droplet leading to the spreading phenomenon. For the polymer PAM-18Na, it is possible that a specific orientation of the comonomeric groups on the surface tablets with respect to the polymer occurs, where at low proportions (10% and 20%), the alkyl chains locate inwardly, leaving the carboxylate groups out of the surface, turning it more hydrophilic, while at higher proportions (30% and 40%), the effect is the opposite, and the surface becomes hydrophobic, as previously described for the polymer PAM-18K [ 27 ]. For the polymer PAM-4Na, the alkyl chain length is not large enough to generate a hydrophobic repulsion as marked as with the polymer PAM-18Na; thus, the θ c observed is below 90°, indicating that the hydrophobicity degree of the tablet surface does not vary considerably [ 34 , 35 , 36 ].…”

Franz Diffusion Cell Approach for Pre-Formulation Characterisation of Ketoprofen Semi-Solid Dosage Forms

“…Releasing efficiency was defined in terms of the mass flux ( J ) [ 21 , 22 ], which describes the change of drug permeation with respect to time in aqueous systems. In our study, the mass flux (mol·cm −2 ·h −1 ) was determined using the AUC of the permeation profile recorded at a specific time interval and is related to the rectangular area ( R ) described by 100% of the permeation process at the same time interval (24 h).…”

“…When n equals 0.5, the equation becomes equal to the Higuchi model, indicating that the release mechanism is of a Fickian type (case I), whereas values of n between 0.5 and 1.0 suggest that the release mechanism corresponds to an anomalous (non-Fickian) transport. Values of 1.0 indicate that the release mechanism is similar to a zero-order release, whereas values of n greater than 1.0 (Super Case II transport) suggest a drug release process dependent on the relaxation of the polymer chains in the matrix, passing from a vitreous state (lower kinetic movement and increased potential energy) to a relaxed state rubber type (high kinetic movement and lower potential energy) [ 22 , 27 ].…”