Purpose: Incompatibility between drugs and excipients can alter stability and bioavailability of drugs thereby affecting an actives safety and/or efficacy. The purpose of this investigation was to study the compatibility of α, α-xylene-p-bis- 3,3(hydroxyiminomethyl) pyridinium dibromide, (3 PApxy) with a number of commonly used excipients. Methods: Solid dosage forms typically contain diluents, disintegrants, polymers, glidants and lubricants and therefore the compatibility of 3 PApxy with selected excipients from each group was investigated. TGA of Perkin Elmer equipped with Pyris Manager™ software and Mettler Toledo Differential Scanning Calorimeter (DSC). Excipients used were Sodium Laurel Sulphate (SLS), Methyl Cellulose (MC), Hydroxy Propyl methyl cellulose (HPMC), Cellulose acetate (CA), Hydroxy Propyl Cellulose (HPC), Carboxy methyl cellulose (CMC), Ethyl Cellulose (EC), Poly Acryl Amide (PAA), Poly Vinyl Alcohol (PVA), Methyl Paraben (MP), Micro Crystalline Cellulose (MCC), Cetyl trimethyl Ammonium Bromide (CTAB) and Acacia were purchased from Sigma-Aldrich and Alfa-Aesar (USA) and used as such. Results: TGA analysis shows seven out of fourteen excipients, SLS, Betain CMC, MCC, EC, PAA and acacia are found to decrease the thermal stability of drug. The DSC thermogram of 3 PApxy showed a sharp endothermic peak at 267 °C corresponding to its melting point. The DSC thermograms of 3 PApxy and each of the investigated excipients with 1:1 mixtures of 3 PApxy and excipients were compared. On the basis of DSC results, 3 PApxy was found to be compatible with all excipients except SLS. Conclusion: Based on TGA and DSC studies, 3 PApxy was found to be compatible with most commonly used excipients except for SLS. These studies may be relevant when formulating novel dosage form systems for 3 PApxy.
Keywords: 3 PApxy, Antidotes for chemical warfare agents, Incompatibility, Differential scanning calometry, Drug excipient interaction, Initial decomposition temperature, Organophosphorus compounds, Oximes, Preformulation study, Thermaogravimetry, Thermoanalytical techniques
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