RESUMO
The hydrogel system of poly(methacrylic acid-co-N-vinyl pyrrolidone) was evaluated for use as an oral delivery system for growth hormone and salmon calcitonin. These proteins were selected because of their therapeutic importance and the insight provided by evaluating the delivery of a therapeutic agent with a high molecular weight (growth hormone) and a drug with a high isoelectric point (salmon calcitonin). Growth hormone loading and release studies were performed for both P(MAA-co-NVP) and P(MAA-g-PEG). Loading efficiencies for the respective systems were 50.9 ± 1.8% and 57.8 ± 4.1%; weight incorporation of the protein was determined to be 3.5 ± 0.1% and 4.0 ± 0.3%. At pH 7.4, growth hormone release of 90% occurred within 45 min for P(MAA-co-NVP) microparticles; 90% release was not achieved with P(MAA-g-PEG) microparticles until 180 min. At pH 1.2, no release occurred from P(MAA-co-NVP) microparticles but 10% release occurred from P(MAA-g-PEG) microparticles. Salmon calcitonin loading and release were shown to be affected by the negative charges of deprotonated MAA; for systems with monomer molar feed ratios of 4:1, 1:1 and 1:4 MAA:NVP, loading efficiencies were determined to be 70.6 ± 3.0%, 25.3 ± 1.2%, and 1.6 ± 1.3%. Salmon calcitonin release was minimal from the copolymer with 4:1 MAA:NVP monomer feed at pH 7.4. The release improved when the pH was raised above physiological levels. These studies confirmed that P(MAA-co-NVP) was an effective oral delivery system for high molecular weight drugs, but improvements are needed before the system could be utilized for high isoelectric point therapeutic delivery.
RESUMO
Different interpolymer complexes (IPCs) of chitosan (CS) and carboxymethylcellulose sodium salt (CMC) were used to elaborate mini-matrices containing clarithromycin (CAM). IPCs were characterized by FTIR, DSC and powder X-ray (XRD). Compression processes did not modify the physical state of CAM which was in its polymorph Form II. However, during tableting, polymer/polymer interactions occurred to form matrix systems that were confirmed by DSC. When mini-matrices were placed in acetate buffer (pH 4.2), the formation of a CAM solvate was determined by XRD, FTIR and DSC, showing the presence of incorporated crystallizing solvent molecules. Grazing incidence X-ray diffraction (GID) enabled us to profile transformations of CAM on surfaces of mini-matrices when it is in intimate contact with dissolution medium, and its conversion to a solvate form prior to its dissolution process. Besides, FTIR and DSC revealed polymer-polymer electrostatic interactions during dissolution process. Furthermore, swelling and eroding studies and in vitro drug release exhibited that when increasing the amount of CS within IPCs, swelling and erosion rates were greater and CAM release was faster. Zero-order kinetics from drug release profiles were related to linear erosion kinetics, and highlighted that erosion played an important role in drug release due to CAM poor solubility at this pH.