Modeling the effects of storage temperature excursions on shelf life

Currently available cyanide antidotes must be given by intravenous injection over 5–10 min, making them illsuited for treating many people in the field, as could occur in a major fire, an industrial accident, or a terrorist attack. These scenarios call for a drug that can be given quickly, e.g., by intramuscular injection. We have shown that aquohydroxocobinamide is a potent cyanide antidote in animal models of cyanide poisoning, but it is unstable in solution and poorly absorbed after intramuscular injection. Here we show that adding sodium nitrite to cobinamide yields a stable derivative (referred to as nitrocobinamide) that rescues cyanide-poisoned mice and rabbits when given by intramuscular injection. We also show that the efficacy of nitrocobinamide is markedly enhanced by coadministering sodium thiosulfate (reducing the total injected volume), and we calculate that ∼1.4 mL each of nitrocobinamide and sodium thiosulfate should rescue a human from a lethal cyanide exposure.

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“…The accelerated degradation data can be extrapolated to a nitrocobinamide solution being stable for at least 1 year at room temperature. 21,24 …”

Section: Resultsmentioning

confidence: 99%

Nitrocobinamide, a New Cyanide Antidote That Can Be Administered by Intramuscular Injection

Chan¹,

Jiang²,

Fridman³

et al. 2015

J. Med. Chem.

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“…Evaluation of stability is an essential part of the assessment of the vaccine quality. Indeed, the stability studies are aimed at verifying that the vaccines maintain their efficacy/ quality criteria throughout their shelf lives [14]. Worth mentioning that excursions from storage condition requirements may affect product performance and stability.…”

Section: Discussionmentioning

confidence: 99%

A Comparative Approach on Shelf Life Stability of Tetanus Toxoid Vaccine Produced from Imported and Locally Formulated Bulk in Private Sector Facility of Pakistan

Abolghasemi¹,

Kulsum²

2016

IJVR

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Hassan A K, Kulsum A, Hassan A U (2016) A comparative approach on shelf life stability of tetanus toxoid vaccine produced from imported and locally formulated bulk in private sector facility of Pakistan. AbstractTetanus is an acute ailment, pictured by the substantial increase in rigidity and spastic cramps in striated muscle. The substandard tetanus toxoid vaccine might increase the incidence of neonatal tetanus. WHO has taken many steps to help national regulatory authorities and vaccine manufacturers to make sure its quality and efficacy. It has developed international principles of stability analysis of every vaccine that is available in the form of recommendations and guidelines. The aim of the present study was to ensure the efficacy of tetanus vaccine produced by manufacturer of private sector (Amson Vaccine and Pharma (Pvt) LTD. Islamabad, Pakistan). All stability studies performed on final products stored at 2-8⁰C and evaluated at near expiry and even three months after its expiry month. The study gives efficacy comparison between Tetanus vaccine injection filled from imported RTF Bulk and Formulated Tetanus Toxoid Bulk from the private sector. The findings indicate that the formulated tetanus vaccine is equally effective when checked its safety profile in live animals. The study also reveals that the product remains stable till last day of its expiry month provided if the cold chain was maintained between 2 -8⁰C till consumed.Keywords: Shelf Life Studies; Tetanus Toxoid; Pakistan. Citation: Hassan A K, Kulsum A, Hassan A U (2016) A comparative approach on shelf life stability of tetanus toxoid vaccine produced from imported and locally formulated bulk in private sector facility of Pakistan.

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“…

\ln (italick) = \ln (italicA) - \frac{E_{a}}{italicRT}

Where, k is the degradation rate constant, A is the frequency factor, E a is the activation energy, R is the gas constant and T is the absolute temperature in degrees Kelvin. The k value depends on the E a and is characteristic of a specific compound …”

Section: Methodsmentioning

confidence: 99%

“…The significance of the E a value is to determine the temperature dependency of a chemical reaction. The higher the value of E a for a chemical reaction the greater the acceleration with increase in temperature and the more the stability of a drug is temperature dependent . Generally, drugs with lower E a values have significantly longer shelf‐lives .…”

Section: Methodsmentioning

confidence: 99%

Evaluation of degradation kinetics and physicochemical stability of tenofovir

Agrahari

Putty

Mathes

et al. 2014

Drug Testing and Analysis

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Tenofovir (TFV) has been proven to prevent the transmission of the Human Immunodeficiency Virus (HIV) through the vagina. But, there is little information available about its stability under various storage and stress conditions. Hence, this study aimed to investigate the degradation behavior and physicochemical stability of TFV using liquid chromatography coupled mass spectrometry (LC-MS) and solid state X-ray diffraction (XRD) analyses. The LC-MS analysis was performed on a QTrap mass spectrometer with an enhanced mass spectrum (EMS) scan in positive mode. A reversed phase C18 column was used as the stationary phase. TFV exhibited degradation under acidic and alkaline hydrolytic conditions. The degradation products with m/z 289.2 and 170 amu have been proposed as 6-Hydroxy adenine derivative of TFV, and (2-hydroxypropan-2-yloxy) methylphosphonic acid, respectively. A pseudo-first-order degradation kinetic allowed for estimating the shelf-life, half-life, and time required for 90% degradation values of 3.84,25.34, and 84.22 h in acidic conditions, and 58.26,384.49, and 1277.75 h in alkaline conditions, respectively. No significant degradation was observed at pH 4.5 (normal cervicovaginal pH) and oxidative stress conditions of 3% and 30% v/v hydrogen peroxide solution. The shelf life of TFV powder at room temperature was 23 months as calculated by using an Arrhenius plot. The XRD pattern showed that the drug was stable and maintained its original crystallinity under the accelerated and thermal stress conditions applied. Stability analyses revealed that the TFV was stable in various stress conditions; however, formulation strategies should be implemented to protect it in strong acidic and alkaline environments.

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Modeling the effects of storage temperature excursions on shelf life

Cited by 14 publications

References 9 publications

Nitrocobinamide, a New Cyanide Antidote That Can Be Administered by Intramuscular Injection

Nitrocobinamide, a New Cyanide Antidote That Can Be Administered by Intramuscular Injection

A Comparative Approach on Shelf Life Stability of Tetanus Toxoid Vaccine Produced from Imported and Locally Formulated Bulk in Private Sector Facility of Pakistan

Evaluation of degradation kinetics and physicochemical stability of tenofovir

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