ABSTRACT
Formulation/pharmaceutical excipients play a major role in formulating drug candidates, with the ob-jectives of ease of administration, targeted delivery and complete availability. Many excipients used in pharmaceutical formulations are orphanized in preclinical drug discovery. These orphan excipients could enhance formulatability of highly lipophilic compounds. Additionally, they are safe in preclinical species when used below the LD50 values. However, when the excipients are used in formulating compounds with diverse physico-chemical properties, they pose challenges by modulating study results through their bioanalytical matrix effects. Excipients invariably present in study samples and not in the cali-bration curve standards cause over-/under- estimation of exposures. Thus, the mechanism by which excipients cause matrix effects and strategies to nullify these effects needs to be revisited. Furthermore, formulation excipients cause drug interactions by moderating the pathways of drug metabolizing en-zymes and drug transport proteins. Although it is not possible to get rid of excipient driven interactions, it is always advised to be aware of these interactions and apply the knowledge to draw meaningful conclusions from study results. In this review, we will comprehensively discuss a) orphan excipients that have wider applications in preclinical formulations, b) bioanalytical matrix effects and possible ap-proaches to mitigating these effects, and c) excipient driven drug interactions and strategies to alleviate the impacts of drug interactions.
ABSTRACT
Extraction of tooth leads to alveolar ridge resorption, which is more pronounced in the 1st year after extraction. Ridge resorption results in loss of interdental papillae and creation of unesthetic black triangles. Root submergence technique (RST) is a procedure where the tooth is decoronated and submerged at or below the alveolar bone level. The goal of the technique is to maintain the attachment complex of the tooth, which will prevent the alveolar bone resorption at the site with maintained soft tissue profile resulting in better esthetic results. The present case describes a relatively bloodless and minimally invasive modified RST that can be implemented in routine clinical practice with the predictable esthetic outcome.
ABSTRACT
A rapid, sensitive and selective pseudoMRM (pMRM)-based method for the determination of solutol HS15 (SHS15) in rat plasma was developed using liquid chromatography/tandem mass spectro-metry (LC–MS/MS). The most abundant ions corresponding to SHS15 free polyethyleneglycol (PEG) oligomers at m/z 481, 525, 569, 613, 657, 701, 745, 789, 833, 877, 921 and 965 were selected for pMRM in electrospray mode of ionization. Purity of the lipophilic and hydrophilic components of SHS15 was estimated using evaporative light scattering detector (ELSD). Plasma concentrations of SHS15 were measured after oral administration at 2.50 g/kg dose and intravenous administration at 1.00 g/kg dose in male Sprague Dawley rats. SHS15 has poor oral bioavailability of 13.74% in rats. Differences in pharmacokinetics of oligomers were studied. A novel proposal was conveyed to the scientific community, where formulation excipient could be analyzed as a qualifier in the analysis of new chemical entities (NCEs) to address the spiky plasma concentration profiles.
ABSTRACT
Reactive oxygen species are a part of the normal physiology of the biological system but their subsequent defence undergoes alteration during diseased conditions. Administration of anaesthesia for surgery may also alter the formation of reactive oxygen species. The present work deals with the comparative status of oxidative stress (lipid peroxidation) and anti-oxidant defence markers (superoxide dismutase and catalase) in blood in 3 groups of 15 patients each receiving halothane, relaxant vecuronium and spinal form of anaesthesia with lignocaine 5% heavy. The results obtained depict that the formation of malonyl dialdehyde as well as decrease in superoxide dismutase and catalase activities was highest in spinal anaesthesia followed by halothane and then relaxant group. Therefore, it seems important to consider the pre-operative anti-oxidant status while administering anaesthesia to such patients in order to provide biologically safe anaesthesia.