Home About us Contact
|
Home About us Contact | ||
|
|
||
Stability Profiles (stability + profile)
Selected AbstractsStability profiles of drug products extended beyond labeled expiration datesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2006Robbe C. Lyon Abstract The American Medical Association has questioned whether expiration dating markedly underestimates the actual shelf life of drug products. Results from the shelf life extension program (SLEP) have been evaluated to provide extensive data to address this issue. The SLEP has been administered by the Food and Drug Administration for the United States Department of Defense (DOD) for 20 years. This program probably contains the most extensive source of pharmaceutical stability data extant. This report summarizes extended stability profiles for 122 different drug products (3005 different lots). The drug products were categorized into five groups based on incidence of initial extension failures and termination failures (extended lot eventually failed upon re-testing). Based on testing and stability assessment, 88% of the lots were extended at least 1 year beyond their original expiration date for an average extension of 66 months, but the additional stability period was highly variable. The SLEP data supports the assertion that many drug products, if properly stored, can be extended past the expiration date. Due to the lot-to-lot variability, the stability and quality of extended drug products can only be assured by periodic testing and systematic evaluation of each lot. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1549,1560, 2006 [source] Relationship between atmospheric circulation types over Greece and western,central Europe during the period 1958,97INTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 14 2004Christina Anagnostopoulou Abstract An attempt is made to examine the relationship of the surface circulation prevailing over Europe with the corresponding surface and 500 hPa over Greece by correlating Lamb weather types for western Europe and Hess and Brezowsky (HB) types for central Europe with those derived from a new classification scheme for the Greek area. It was found that it was difficult to formulate rules controlling the frequency distributions of the circulation types over the Greek area in relation to the circulation over western and central Europe. However, statistically significant correlation was found between certain types with high frequency, which is greater between Lamb and HB types with the surface circulation types over the Greek area, compared with 500 hPa circulation types. For the most correlated pairs, seasonal composites of mean sea-level pressure and 500 hPa geopotential height anomalies demonstrated that the formation of the circulation types over the Greek area depends on the extent, intensity of the anticyclonic or cyclonic centres, air mass characteristics, and stability profile in the lower troposphere over the regions examined, but especially over the central and eastern Mediterranean. Copyright © 2004 Royal Meteorological Society [source] The Proteolytic Stability of ,Designed' , -Peptides Containing , -Peptide-Bond Mimics and of Mixed ,,, -Peptides: Application to the Construction of MHC-Binding PeptidesCHEMISTRY & BIODIVERSITY, Issue 5 2005David Whereas , -peptides are rapidly degraded in vivo and in vitro by a multitude of peptidases, substrates constructed entirely of or incorporating homologated , -amino acid (i.e., , -amino acid) units exhibit a superior stability profile. Efforts made so far to proteolytically hydrolyze a ,, peptide bond have not proved fruitful; a study aimed at breaching this proteolytic stability is discussed here. A series of such bonds have been designed with side-chain groups similar in relative positions (constitution) and three-dimensional arrangements (configuration) as found about , -peptidic amide bonds. Increasing the prospect for degradation would permit the tuning of , -peptide stability; here, however, no cleavage was observed (1, 2, 4,6, Table,1). Peptides comprised of , - and , -amino acids (mixed ,,, -peptides, 8,11) are expected to benefit from both recognition by a natural receptor and a high level of proteolytic stability, ideal characteristics of pharmacologically active compounds. ,3 -Peptides containing , -amino acid moieties at the N-terminus are degraded, albeit slowly, by several peptidases. Of particular interest is the ability of pronase to cleave an ,, peptide bond, namely that of ,Ala,3hAla. Significantly, successful hydrolysis is independent of the configuration of the , -amino acid. Some of the ,,, -peptides discussed here are being investigated for their binding affinities to class I MHC proteins. The computer-programming steps required to prepare ,,, -peptides on an automated peptide synthesizer are presented. [source] Papillary and muscle invasive bladder tumors with distinct genomic stability profiles have different DNA repair fidelity and KU DNA-binding activitiesGENES, CHROMOSOMES AND CANCER, Issue 4 2009Johanne Bentley Low-grade noninvasive papillary bladder tumors are genetically stable whereas muscle invasive bladder tumors display high levels of chromosomal aberrations. As cells deficient for nonhomologous end-joining (NHEJ) pathway components display increased genomic instability, we sought to determine the NHEJ repair characteristics of bladder tumors and correlate this with tumor stage and grade. A panel of 13 human bladder tumors of defined stage and grade were investigated for chromosomal aberrations by comparative genomic hybridization and for NHEJ repair fidelity and function. Repair assays were conducted with extracts made directly from bladder tumor specimens to avoid culture-induced phenotypic alterations and selection bias as only a minority of bladder tumors grow in culture. Four noninvasive bladder tumors (pTaG2), which were genetically stable, repaired a partially incompatible double-strand break (DSB) by NHEJ-dependent annealing of termini and fill-in of overhangs with minimal loss of nucleotides. In contrast, four muscle invasive bladder cancers (pT2-3G3), which displayed gross chromosomal rearrangements, repaired DSBs in an error-prone manner involving extensive resection and microhomology association. Four minimally invasive bladder cancers (pT1G3) had characteristics of both repair types. Error-prone repair in bladder tumors correlated with reduced KU DNA-binding and loss of TP53 function. In conclusion, there were distinct differences in DSB repair between noninvasive papillary tumors and higher stage/grade invasive cancers. End-joining fidelity correlated with stage and was increasingly error-prone as tumors became more invasive and KU binding activity reduced; these changes may underlie the different genomic profiles of these tumors. © 2008 Wiley-Liss, Inc. [source] Stability profiles of drug products extended beyond labeled expiration datesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2006Robbe C. Lyon Abstract The American Medical Association has questioned whether expiration dating markedly underestimates the actual shelf life of drug products. Results from the shelf life extension program (SLEP) have been evaluated to provide extensive data to address this issue. The SLEP has been administered by the Food and Drug Administration for the United States Department of Defense (DOD) for 20 years. This program probably contains the most extensive source of pharmaceutical stability data extant. This report summarizes extended stability profiles for 122 different drug products (3005 different lots). The drug products were categorized into five groups based on incidence of initial extension failures and termination failures (extended lot eventually failed upon re-testing). Based on testing and stability assessment, 88% of the lots were extended at least 1 year beyond their original expiration date for an average extension of 66 months, but the additional stability period was highly variable. The SLEP data supports the assertion that many drug products, if properly stored, can be extended past the expiration date. Due to the lot-to-lot variability, the stability and quality of extended drug products can only be assured by periodic testing and systematic evaluation of each lot. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1549,1560, 2006 [source] Anthrax vaccine powder formulations for nasal mucosal deliveryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2006Ge Jiang Abstract Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and formulation development of such powder formulations. The physical stability of rPA was studied in solution as a function of pH and temperature using circular dichroism (CD), and UV-visible absorption and fluorescence spectroscopies. Extensive aggregation of rPA was observed at physiological temperatures. An empirical phase diagram, constructed using a combination of CD and fluorescence data, suggests that rPA is most thermally stable within the pH range of 6,8. To identify potential stabilizers, a library of GRAS excipients was screened using an aggregation sensitive turbidity assay, CD, and fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7,8 using trehalose as stabilizer and a CpG-containing oligonucleotide adjuvant. SFD formulations displayed substantial improvement in storage stability over liquid formulations. In combination with noninvasive intranasal delivery, such powder formulations may offer an attractive approach for mass biodefense immunization. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:80,96, 2006 [source] Characterization of the interactions between polymethacrylate-based aqueous polymeric dispersions and aluminum lakesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2001Nasser Nyamweya Abstract Instability in film coating formulations can arise from interactions between aluminum lake pigments and aqueous polymeric dispersions. The purpose of this study was to characterize the interactions between three polymethacrylate-based aqueous polymeric dispersions (Eudragit® RS 30 D, Eudragit® L 30 D-55, and Eudragit® NE 30 D) and aluminum lakes. Particle size measurements, pH stability profiles, zeta potential measurements, and microscopy were used to study mixed dispersions of the polymeric latices and the lakes. Interactions leading to dispersion instability were related to the surface charge of the components in the formulation. Interactions between the ionic polymers and the lakes arose from instability of the lakes outside a certain pH range resulting in the release of electrolytes, which led to aggregation of the polymeric particles. Interactions between the nonionic polymer and the lakes were related to the polymer modifying the surface charge of the lakes, resulting in aggregation of the pigment particles. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1937,1947, 2001 [source] Expression of a Phanerochaete chrysosporium Manganese Peroxidase Gene in the Yeast Pichia pastorisBIOTECHNOLOGY PROGRESS, Issue 5 2003Lina Gu A gene encoding manganese peroxidase (mnp1) from Phanerochaetechrysosporium was cloned downstream of a constitutive glyceraldehyde-3-phosphate dehydrogenase promoter in the methylotrophic yeast Pichia pastoris. Three different expression vectors were constructed: pZBMNP contains the native P.chrysosporium fungal secretion signal, p,AMNP contains an ,-factor secretion signal derived from Saccharomyces cerevisiae, and pZBIMNP has no secretion signal and was used for intracellular expression. Both the native fungal secretion signal sequence and ,-factor secretion signal sequence directed the secretion of active recombinant manganese peroxidase (rMnP) from P. pastoris transformants. The majority of the rMnP produced by P. pastoris exhibited a molecular mass (55,100 kDa) considerably larger than that of the wild-type manganese peroxidase (wtMnP, 46 kDa). Deletion of the native fungal secretion signal yielded a molecular mass of 39 kDa for intracellular rMnP in P. pastoris. Treatment of the secreted rMnP with endoglycosidase H (Endo H) resulted in a considerable decrease in the mass of rMnP, indicating N-linked hyperglycosylation. Partially purified rMnP showed kinetic characteristics similar to those of wtMnP. Both enzymes also had similar pH stability profiles. Addition of exogenous MnII, CaII, and FeIII conferred additional thermal stability to both enzymes. However, rMnP was slightly less thermostable than wtMnP, which demonstrated an extended half-life at 55 °C. [source] | ||||||||||