Extemporaneous Isoniazid Mixture: Stability Implications

Abstract

Background: Isoniazid mixtures are compounded in Australia using commercially available isoniazid tablets. Aim: To determine the stability of isoniazid 10 mg/mL mixture compounded from commercially available isoniazid tablets. Method: The stability of the compounded isoniazid mixture stored at a range of temperatures (4-60 °C) was assessed with high performance liquid chromatography. Differential scanning calorimetry was used to investigate the compatibility of isoniazid with the excipient, lactose. Results: The compounded isoniazid mixture exhibited significant degradation (≥ ≥ ≥ ≥ ≥ 10% after 3 days at 4 and 25 ºC), whereas the control (using isoniazid powder) retained desired stability (> 90% at 30 days) under identical conditions. A replicate control formulation, spiked with lactose, produced statistically similar degradation profiles to that of the compounded isoniazid mixture (p > 0.05), indicating lactose to be responsible for the degradation of isoniazid. The thermoanalytical studies demonstrated an incompatibility between isoniazid and lactose (broadening and shifting of melting endotherm of isoniazid at 171.46 ºC). Conclusion: The British Pharmaceutical Codex specifies the use of isoniazid powder for compounding isoniazid mixture. This study highlights the importance for stability evaluations on all modified extemporaneous preparations in order to ensure that quality pharmaceuticals are delivered to patients. J Pharm Pract Res 2005; 35: 181-2.

Exploring the Structural Chemistry of Pyrophosphoramides: N,N′,N″,N‴-Tetraisopropylpyrophosphoramide

“…The crystal structure of the mono-N-substituted pyrophosphoramide, O((iPrNH) 2 PO) 2 1 has been determined from single-crystal X-ray diffraction data while the chemical identity of the species was supported by IR, 1 H NMR, 31 P NMR, and GC MS data (see SI). A thorough structural comparison of 1 with other pyrophosphoramides for which the crystal structures have been published previously was carried out.…”

“…This is important for mono-N-substituted pyrophosphoramides given their possible use as a pesticide. The formation of different forms with different thermodynamic and kinetic stabilities can aid in complexation reactions and e.g., diminish decomposition on storage, a property of great importance for use in agriculture [28,29,31,32].…”

“…FT-IR (Fourier Transform Infrared) spectra were recorded using KBr pellet samples and a Shimadzu IRAffinity-1 FTIR spectrophotometer. 1 H NMR and 31 P NMR (Nuclear Magnetic Resonance) spectra were collected on a Bruker Ascend NMR spectrometer with a probe having a set frequency of 500.13 MHz for 1 H NMR and 202.457 MHz for 31 P NMR. Gas chromatography Mass spectroscopy (GC MS) data was collected using a Thermo DSQ II GC/MS spectrometer with samples being prepared by dissolution of the products in chloroform.…”

Quality Assurance of Medicines in Practice

“…This was demonstrated in a study investigating the stability of an isoniazid (INH) liquid prepared using commercially available tablets and a British Pharmaceutical Codex (BPC) formula, where significant degradation of the INH (≥ 10 % after 3 days at both 4 and 25 ºC) was shown whereas the control (using pure INH powder) retained the desired stability of > 90 % after 30 days, as specified in the BPC, under identical conditions (Haywood, Mangan et al, 2005). A replicate control formulation spiked with lactose (an excipient present in the commercial tablets), produced similar degradation profiles to that of the compounded oral liquid.…”

Isoniazid loaded gelatin-cellulose whiskers nanoparticles for controlled drug delivery applications

“…Isoniazid, an anti-tuberculosis drug, has been used as a model drug for controlled delivery applications. 10 In recent days, emphasis is given to prepare nanoparticles for the controlled delivery of different active agents or drugs such as proteins, genes, peptides, etc. 11 13 Nanoparticles can be prepared from different natural biodegradable polymers, polysaccharides, proteins, etc.…”