ABSTRACT
For the purpose of establishing the optimum processing parameters and storage conditions associated with nanolipid formulations of the artemisinin derivative artesunate, it was necessary to evaluate the thermal stability and solubility profiles of artesunate in aqueous solutions at various temperatures and pH. The effect of increased temperature and humidity on artesunate was determined by storing samples of the raw material in a climate chamber for 3 months and analyzing these by an established HPLC method. Artesunate remained relatively stable during storage up to 40°C ± 0.5°C and 75% relative humidity for 3 months, wherein it undergoes approximately 9% decomposition. At higher temperatures, substantially greater decomposition supervenes, with formation of dihydroartemisinin (DHA) and other products. In solution, artesunate is relatively stable at 15°C with less than 10% degradation over 24 h. The aqueous solubility of artesunate at different pH values after 60 min are pH 1.2 (0.1 M HCl) 0.26 mg/mL, pH 4.5 (acetate buffer) 0.92 mg/mL, distilled water 1.40 mg/mL, and pH 6.8 (phosphate buffer) 6.59 mg/mL, thus relating to the amount of ionized drug present. Overall, for optimal preparation and storage of the designated formulations of artesunate, relatively low temperatures will have to be maintained throughout.
Subject(s)
Water , Artesunate , Solubility , Water/chemistry , Drug StabilityABSTRACT
Previous isothermal microcalorimetry studies at 40 °C, with and without humidity (RH 75%), had shown no incompatibility between rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol HCl (EMB). The purpose of this study was to explore any interactions at an increased temperature of 50 °C and also to investigate the possibility of incompatibilities between the drugs and tablet excipients used in the most commonly prescribed commercial four-drug TB FDC. No incompatibilities were observed between the excipients, or when the excipients were tested with the four drugs individually. Incompatibility was observed with the four drugs combined.
Subject(s)
Antitubercular Agents/chemistry , Calorimetry , Excipients/chemistry , Ethambutol/chemistry , Isoniazid/chemistry , Pyrazinamide/chemistry , Rifampin/chemistryABSTRACT
Some known nevirapine solvates have been reported to undergo solvent exchange in aqueous media to form a stable hemihydrate. This study aimed to determine the effects of atmospheric moisture on said nevirapine solvates and to gain insight into which factors determine the end product of transformation. Solvates were prepared by solvent recrystallisation and stored, together with the anhydrous and hemihydrate forms, in a climate chamber at 40 °C and 75% RH for a period of 28 days. Samples were analyzed using DSC, TGA, FT-IR, PXRD and Karl Fischer titration. Some solvates were observed to undergo desolvation to the anhydrous form of nevirapine (Form I), whilst others converted to the hemihydrate. It was found that water miscibility of the guest solvent determined the stable form of nevirapine, anhydrous or hemihydrate, to which each solvate eventually transformed. Transformation to the hemihydrate only occurred if the guest solvent was sufficiently water soluble to allow water molecules to enter solvent channels and displace the original guest. Solvates with hydrophobic guests desolvated to the anhydrous form. We concluded that, in the absence of a guest, solvent channels are lost during transformation to the monoclinic crystal system and space group P21/c (Form I) so that water cannot enter after desolvation.
Subject(s)
Anti-HIV Agents/chemistry , Nevirapine/chemistry , Crystallization , Hot Temperature , Humidity , Hydrophobic and Hydrophilic Interactions , Models, Molecular , Molecular Weight , Thermogravimetry , Water/chemistryABSTRACT
Water and water vapor are the bane of amorphous drug stability, both in storage and after administration. As is to be expected, crystallization of amorphous azithromycin did occur when exposed to water as dissolution medium. However, experimental results showed that, although solution-mediated phase transformation had occurred, it was not a rapid process for this drug. It is considered to be an advantageous characteristic of amorphous azithromycin and likely due to the high molecular mass (748.984 g/mol) and complex structure necessitating more energy for transformations to occur. A high apparent solubility is maintained for a considerable period of time, potentially rendering a higher percentage of this BCS Class II drug available for absorption when administered orally.
Subject(s)
Azithromycin/chemistry , Chemistry, Pharmaceutical/methods , Water/chemistry , Azithromycin/administration & dosage , Crystallization , Drug Stability , Drug Storage , Pharmaceutical Solutions , SolubilityABSTRACT
An UV spectrophotometric method was developed for the quantitative determination of nevirapine in water, methanol and 0.1 N HCl. It was found that qualitative determination is also possible, due to a peak-shift observed with 0.1 N HCl. The solubility at 37 degrees C, for both the anhydrous and Hemihydrated forms of nevirapine, was determined in each of the three solvents.
