Stability Articles

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 this study was to prepare poly(ethylene glycol) (PEG)ylated octreotide and investigate the stability against acylation by polyester polymers such as poly(lactic acid) and poly(lactic-co-glycolic acid). Octreotide was modified by reaction with monomethoxy PEG-propionaldehyde (molecular weight 5,000) in the presence of sodium cyanoborohydride. The mono-PEGylated fraction was isolated by reversed-phase high-performance liquid chromatography (HPLC) and characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Circular dichroism demonstrated no significant secondary structural differences between mono-PEGylated octreotide (mono-PEG-octreotide) and intact octreotide. As a test system for the stability study against acylation reaction, lactic acid (LA) solutions with various concentrations and pH values were prepared with water dilution and subsequent accelerated equilibration at 90°C for 24 hours.

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

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?

A simple HPLC procedure is described for the determination of bendroflumethiazide (BFMT) in pharmaceutical formulations and urine samples. No interferences from common additives or other drugs frequently administered with BFMT or from endogenous compounds in urine samples were found. The lack of an organic solvent in the mobile phase reduces the risk of environmental contamination and human toxicity.

Bendroflumethiazide (BFMT: (RS)-3-phenylmethyl-3,4- dihydro-6-trifluoromethyl-2H-1,2,4-benzothiadiazine-7- sulphonamide-1,1-dioxide) is a potent diuretic drug extensively used for the treatment of hypertension and oedema that belongs to the thiazide family.1 BMFT is well absorbed from the gastrointestinal tract after oral administration and the absorption is not affected by food. It lowers blood pressure and removes extra salt and water from the body by acting on the kidneys. BFMT is usually prescribed as tablets and frequently in combination with
-blockers.

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.

Jim Jiao, Diane J. Burgess
AAPS PharmSci. 2003; 5 (1):

Allen C. Templeton, PhD, et al
Pharmaceutical Technology, Mar 2, 2005
The authors evaluate the implications of product photosensitivity and how it influences various aspects of product development.They discuss a product photosensitivity classification system and present a photosensitive pharmaceutical product case study. Photostability testing in the pharmaceutical industry has evolved rapidly, particularly since the May 1997 publication of the ICH Q1B guidance “Photostability Testing of New Drug Substances and Products” in the Code of Federal Regulations (hereafter referred to in this article as Q1B) (1).Although some notable criticisms have been leveled against the document for its perceived shortcomings (2–4), Q1B has provided much-needed input to pharmaceutical applicants about regulatory requirements for photostability testing.