M. Mangan

Analysing the crystal purity of mebendazole raw material and its stability in a suspension formulation.

The objective of this study was to develop a simple, direct and non-destructive method to assess crystal purity of mebendazole raw material and to establish its stability in a suspension formulation using diffuse reflectance ultraviolet (DRA-UV) spectroscopy and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. Quantitation of mebendazole, found to exhibit polymorphism with three polymorphic forms A, B and C identified, was carried out with ATR-FTIR spectroscopy. Artificial neural network (ANN) was employed as a data-modelling tool. The developed ANN models confirmed that the characteristic absorptions in the infrared (IR) spectral region are directly proportional to the measured amounts of mebendazole crystal forms present in the samples (r(2)>0.94), which was confirmed with X-ray diffraction (XRD) at r(2)>0.97. These models also predicted that the mebendazole raw material contained 7.21+/-1.25% (ATR-FTIR data) and 10.38+/-0.18% (XRD data) of form A as an impurity. ATR-FTIR data for the suspension formulation showed some dissolution of form C and recrystalisation as the more stable form A. These quantitative results obtained for the binary crystal form mixtures clearly demonstrate the strong potential of ATR-FTIR for use in the determination of the polymorphic content not only in bulk pharmaceuticals but also in liquid formulations.

Stability Implications of Repackaging Paracetamol Tablets into Dose Administration Aids

Despite the widespread use of dose administration aids (DAAs) there is little available data on the stability of drugs during repackaging or storage in these devices.

Stability of Frusemide Tablets Repackaged in Dose Administration Aids

Repackaging tablets into a dose administration aid (DAA) requires that the pharmacist consider the stability of the active pharmaceutical ingredient and the excipients of the drug product. Frusemide is susceptible to photodegradation and is commonly repackaged into DAAs.

Stability of sodium valproate tablets repackaged into dose administration aids

Objectives  Since sodium valproate, a commonly used antiepileptic drug, has been reported to be unstable in the presence of moisture, our objective was to investigate the effect of repackaging into dose administration aids.

Compliance aids and medicine stability: new evidence of quality assurance.

Although increasing use of compliance aids is resulting in improved clinical outcomes for patients, the stability of some drugs being repackaged into these aids is being questioned. This is due to the fact that despite their widespread use, there is limited availability of relevant stability data. This review presents clinical evidence for repackaging into Dose Administration Aids (DAAs), the Australian Pharmaceutical Advisory Committee and other guidelines on general stability issues related to repackaging and a summary of evidence for stability studies conducted in the practice. For frusemide and prochlorperazine chosen as candidates for study because of their light sensitivity, while discoloration on light exposure rendered them unacceptable for patient use, precautions in repackaging and patient counselling can easily overcome this problem. In the case of sodium valproate however, hygroscopicity results in these tablets being unusable after exposure to accelerated storage conditions. In the absence of specific data on the stability of drug products repackaged into compliance aids, the guidelines, practical recommendations for repackaging and the management of compliance aids put forward in this article provide the pharmacist with the tools to make an informed decision on this process.

Prochlorperazine tablets repackaged into dose administration aids: can the patient be assured of quality?

Background and objective:  Patients are increasingly requiring their medications to be repackaged into dose administration aids because of the positive outcomes associated with reduction in medication related hospitalization and adverse effects due to improved medicines management. Since the stability of these repackaged medications is not the responsibility of manufacturer, it is important that drug substances with potential stability issues be identified. Thus the objective of this study was to evaluate the stability of prochlorperazine, a light sensitive drug repackaged into dose administration aids (DAAs), in order to provide guidelines to the pharmacist and advice to the patient on appropriate storage.

Compatibility studies between mannitol and omeprazole sodium isomers

Omeprazole, commonly used in the treatment of various gastrointestinal disorders degrades rapidly in acidic pHs and results in inter-individual variability due to different rates of metabolism amongst patients. Since S-omeprazole shows more predictable bioavailability and excipients have been known to interact with active pharmaceutical ingredients to produce altered bioavailability, it was decided to investigate the compatibility of omeprazole sodium isomers with mannitol, the major excipient in omeprazole formulations using differential scanning calorimetry (DSC) for bulk drug, attenuated total reflectance (ATR) infrared (IR) spectroscopy in a powder mixture and localized thermal analysis (LTA) from a drug disk. DSC results clearly indicate an interaction between mannitol and R-omeprazole sodium due to decreased melting temperatures and broadening peaks. The DSC of S-omeprazole sodium does not show melting temperature although the drug was crystalline. Because of the accelerated temperature conditions during DSC experiments applied in this work, ATR-IR was undertaken to determine whether these results occurred at room temperature for the solid dosage form. The ATR-IR results show a difference between R- and S-omeprazole sodium with mannitol by the appearance of both the amino (N-H) and imino (N-H) stretching frequencies for R-omeprazole and only the N-H for the S-omeprazole sodium. It may thus be concluded that different ratios for the tautomeric forms for S- and R-omeprazole sodium result in changes in the degree of crystallinity and are responsible for the interaction with mannitol, common excipient in formulation. These interactions may be directly related to the difference in terms of bioavailability.

Extemporaneous Isoniazid Mixture: Stability Implications

Isoniazid mixtures are compounded in Australia using commercially available isoniazid tablets.