Characterization of the Pilocarpine:Carbomer complex in aqueous solution

ZOPPI, ARIANA; LONGHI, MARCELA RAQUEL

Ribeirao Preto

Congreso; 7th Internacional Congress of Pharmaceutical Sciences; 2009

INTRODUCTION: Pilocarpine (PIL) is a drug used for the treatment of glaucoma. To obtain an optimal stability of the drug, the eyedrops are formulated at pH 4-5, although in this range of pH the drug is fully ionized, which can reduce the ocular absorption of PIL. It was reported that the use of Carbomer (CBR), a crosslinked poly acrylic acid, was effective for retarding the degradation rate of drugs, through the formation of ionic complexes. Therefore, negatively charged CBR can form an ion pair complex with the positively charged PIL as a tool for the increse of the stability of the drug. OBJECTIVES: The aim of this work was to study the feasibility of a complex of PIL with CRB by an ionic interaction in an aqueous solvent system. METHODS: The specific interactions of PIL with CBR have been studied in aqueous solutions by NMR techniques. All experiments were performed on a Bruker Avance II High Resolution Spectrometer at 400.16 MHz. Induced changes in the  1H chemical shifts for PIL due to its complexation were calculated. due to its complexation were calculated. due to its complexation were calculated. due to its complexation were calculated. Resolution Spectrometer at 400.16 MHz. Induced changes in the  1H chemical shifts for PIL due to its complexation were calculated. due to its complexation were calculated. due to its complexation were calculated. due to its complexation were calculated. Resolution Spectrometer at 400.16 MHz. Induced changes in the  1H chemical shifts for PIL due to its complexation were calculated. due to its complexation were calculated. due to its complexation were calculated. due to its complexation were calculated. Resolution Spectrometer at 400.16 MHz. Induced changes in the  1H chemical shifts for PIL due to its complexation were calculated. due to its complexation were calculated. due to its complexation were calculated. due to its complexation were calculated. RESULTS: In order to study the formation of the PIL:CBR complex, the spectrum of pure PIL was compared to its corresponding signals in the complex. In the presence of CBR, all PIL (Fig. 1) proton resonances were modified, exhibiting downfield displacements with respect to those of the pure drug, therefore this fact was taken as an evidence of complex formation. The protons corresponding to the aromatic ring of PIL (H9, H2’ y H4’) have the most marked downfield displacements, which demonstrated a clear involvement of these hydrogen atoms in PIL:CBR interactions. These downfield displacements have been essentially attributed to the effect caused by the proximity of the carboxylate groups of CBR. The observed changes in the ä of other protons of PIL may arise either as a direct result of a binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. most marked downfield displacements, which demonstrated a clear involvement of these hydrogen atoms in PIL:CBR interactions. These downfield displacements have been essentially attributed to the effect caused by the proximity of the carboxylate groups of CBR. The observed changes in the ä of other protons of PIL may arise either as a direct result of a binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. most marked downfield displacements, which demonstrated a clear involvement of these hydrogen atoms in PIL:CBR interactions. These downfield displacements have been essentially attributed to the effect caused by the proximity of the carboxylate groups of CBR. The observed changes in the ä of other protons of PIL may arise either as a direct result of a binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. most marked downfield displacements, which demonstrated a clear involvement of these hydrogen atoms in PIL:CBR interactions. These downfield displacements have been essentially attributed to the effect caused by the proximity of the carboxylate groups of CBR. The observed changes in the ä of other protons of PIL may arise either as a direct result of a binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug. binding interaction with the macromolecule, or indirectly by a conformational change associated with the interaction. CONCLUSION: Hence, from the experimental results it could be concluded that the formation of an ionic complex between the CBR and PIL is possible. Also, it can allow an increase in the stability of the drug.