Introduction:
Pilocarpine (PIL) is a drug used in the treatment of glaucoma. To obtain an optimal stability of the drug, the eye drops 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 (1). It has been reported that the anionic polyelectrolyte Carbomer (CBR), was effective for retarding the degradation rate of drugs, through the formation of ionic complexes (2, 3). In previous work we reported the positive effect of complexation with CBR on the chemical stability of PIL in aqueous solution (4). The aim of the present study was the preparation and characterization of an ionic complex between PIL and CBR in solid state.
Materials and Methods:
The PIL:CBR complexes were prepared by liophilization or physical mixture of the components. Their interactions were studied in the solid state by fourier-transform infrared spectroscopy (FT-IR), solid state nuclear magnetic resonance (ssNMR), X-ray powder diffraction, scanning electron microscopy (SEM) and thermal analysis (differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)).
Results and Discussion:
When analyzing the FT-IR and ssNMR spectra corresponding to the binary systems prepared by physical mixture or freeze-drying, marked differences are evident with respect to the spectra of the raw materials. These changes are attributed to the complex formation between the drug and the polyelectrolyte thought electrostatic interactions. The powder x-ray diffraction pattern and SEM microphotographs demonstrated that the complexes obtained are amorphous solids. The DSC and TG curves indicated that the binary systems PIL:CBR obtained by physical mixture of the components or liophilization present the same thermal behaviour.
Conclusion:
The anionic polymer CBR showed good capability to interact with the drug PIL giving rise to ionic drug/polymer complex in solid state. The complex can be prepared by physical mixture of the components or liophilization, although the latter method is the best suitable for obtaining this system at industrial scale.
Acknowledgments:
The authors thank the Laboratorios Beta for their donation pilocarpine.
References:
1- Jarvinen K, Jarvinen T, Thompson DO, Stella VJ. The effect of a modified B-cyclodextrin, SBE4-B-CD, on the aqueous stability and ocular absorption of pilocarpine. Curr Eye Res 1994; 13(12): pp. 897-905.
2- Jimenez-Kairuz AF, Allemandi DA, Manzo RH. The improvement of aqueous chemical stability of a model basic drug by ion pairing with acid groups of polyelectrolytes. Int J Pharm 2004; 269(1):149-156.
3- Esteban SL, Manzo RH, Alovero FL. Azithromycin loaded on hydrogels of carbomer: Chemical stability and delivery properties. Int J Pharm 2009; 366(1-2):53-7.
4- Zoppi A, Jim¨¦nez-Kairuz AF, Manzo RH, Longhi MR. Evaluation of aqueous stability of pilocarpine in carbomer hydrogels. VIII Simposio Internacional y III Foro Tecnol¨®gico de la Controlled Release Society. Villa Giardino, Cordoba, Argentina.
