Stability is defined as the capacity of a drug substance or drug product to remain within established specifications to maintain its identity, strength, quality, and purity throughout the retest or expiration dating periods (1). Physical, chemical, and microbiological data are  generated as a function of time and storage conditions (e.g., temperature and relative humidity [RH]). Stability testing provides evidence that the quality of a drug substance or drug product under the influence of various environmental factors changes with time (2). Although the storage conditions are relatively constant, the distribution environment can vary greatly, especially when a drug product is shipped between various climatic zones (1). Seasonal changes, mode of transportation, and the number of drop-off points are also variables that should be considered within the pharmaceutical supply chain.

In the pharmaceutical industry, bulk product characteristics are routinely tested to determine whether the product meets in-house quality assurance specifications. Raw or processed materials are frequently stored in drums or containers. In these instances, one must know how to choose a representative sample that exhibits characteristics similar to those processed by the population as a whole. The common method in statistical practices is choosing a simple random sample from the population.

Once a candidate drug reaches use in humans, all stability storage and testing must be
conducted according to current good manufacturing practices  (CGMPs). The regulatory mandate for stability testing in the United States is contained in 21 CFR Part 211 Section 166, which states that There shall be a written testing program designed to assess the stability characteristics of drug products. The results of such stability testing shall be used in determining appropriate storage conditions and expiration dates. The written program shall be followed and shall include…. Although 21 CFR addresses stability data treatment and reporting for expiration dating, it says almost nothing about how to ensure control within the stability storage operation or how to design stability protocols. There are many ways to run a stability operation in a GMPcompliant manner, but the bottom line is to have written procedures and protocols with documented evidence that they are followed.

Forced degradation or stress testing is undertaken to demonstrate specificity when developing stability-indicating methods, particularly when little information is available about potential degradation products. These studies also provide information about the degradation pathways and degradation products that could form during storage. Forced degradation studies may help facilitate pharmaceutical development as well in areas such as formulation development, manufacturing, and packaging, in which knowledge of chemical behavior can be used to improve a drug product.

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This
study reports on the effects that water absorbed into amorphous sodium
indomethacin (NaIMC) can have on simultaneous tendencies to crystallize
to its trihydrate form and to undergo base-catalyzed hydrolysis because
of the plasticizing effects of water on molecular mobility. Measurement
of water vapor absorption at 30°C and powder x-ray diffraction patterns
as a function of relative humidity (RH) reveal that upon exposure to
21% RH, NaIMC does not crystallize over a 2-month period. Measurements
of the glass transition temperature as a function of such exposure
reveals a change in Tg from 121°C, dry, to 53°C at 21% RH, such that Tg
at 21% RH is ~13°C above the highest storage temperature of 40°C used
in the study. At 56% RH and higher, however, crystallization to the
trihydrate occurs rapidly; although over the 2-month period,
crystallization was never complete. Assessment of chemical degradation

The
purpose of the study was to investigate the effect of hydroxypropyl
beta cyclodextrin (HPβCD) on aqueous solubility, stability, and in
vitro corneal permeation of acyl ester prodrugs of ganciclovir (GCV).
Aqueous solubility and stability of acyl ester prodrugs of Ganciclovir
(GCV) were evaluated in pH 7.4 isotonic phosphate buffer solution
(IPBS) in the presence and absence of HPβCD. Butyryl
cholinesterase-mediated enzymatic hydrolysis of the GCV prodrugs was
studied using various percentage w/v HPβCD. In vitro corneal permeation
of GCV and its prodrugs (with and without 5% HPβCD) across isolated
rabbit cornea was studied using side-by-side diffusion cells.
HPβCD-prodrug complexation was of the AL type with values for
complexation constants ranging between 12 and 108 M-1. Considerable
improvement in chemical and enzymatic stability of the GCV prodrugs was
observed in the presence of HPβCD. The stabilizing effect of HPβCD was

ABSTRACT Nitrendipine, a potent antihypertensive molecule undergoes extensive first-pass metabolism with oral bioavailability in the range from 10% to 20%. The objective of present research investigations was to fabricate an Eudragit E100® pressure sensitive adhesive (PSA)-based stable transdermal therapeutic system (TTS) of nitrendipine, which could deliver drug at a maximum input rate through a transdermal route. Monolithic TTS of nitrendipine was fabricated in Eudragit E100® PSA-based pressure sensitive adhesive. To enhance flux, d-limonene was investigated as a permeation enhancer, and effect of concentration of d-limonene on permeation kinetics of nitrendipine through guinea pig skin was examined. Optimized TTS was evaluated for in-vitro flux though human skin (volar arm) to determine patch size needed to deliver drug through the transdermal route. The optimized TTS was kept for stability study for a period of 1 year at refrigeration, 25?

How do you prove everything is separated?

During the past couple of months, I’ve had several readers write with questions about stability-indicating assays for pharmaceutical products, so I’d like to focus on that topic in this instalment of “LC Troubleshooting.” Stability-indicating assays are some of the most difficult types of liquid chromatography (LC) separations to develop, because chromatographers can’t be sure how many components are present and need to be separated. Let’s look at what these separations are all about and how to develop high-quality assays.
 
Stability Indication If you look at the label on your favourite prescription or over-the-counter pharmaceutical product, you’ll see a use before date. Before this date, the product should remain fully effective under normal storage conditions.