Comparison of two nimodipine formulations in healthy volunteers

Chen

Journal of Food and Drug Analysis

et al. 2017

243

104

Chemical and enzymatic barriers in the gastrointestinal (GI) tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs) are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs.

Section: Oral Delivery Of Slns For Treating Various Diseasesmentioning

confidence: 99%

Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers

Chen

Journal of Food and Drug Analysis

et al. 2017

243

104

“…Venous blood samples were obtained from all the volunteers pre-drug and 1 h after consumption of each tablet on days 1, 3 and 5 to estimate the serum nimodipine concentration. Nimodipine plasma concentration were analyzed by high performance liquid chromatography following the method of the Quin and Gallo [22,58] with two pumps with Diode array detector and programme class LC10. (Stationary phase: C8 250 9 4.6 mm, particle size 5 lm (nucleosyl/100, C8), volume of injection: 100 ml (automatic).…”

Section: Oral Nimodipine Studymentioning

confidence: 99%

Pharmacological enhancement of disc diffusion and differentiation of healthy, ageing and degenerated discs

et al. 2008

Degenerative disc disease (DDD) is still a poorly understood phenomenon because of the lack of availability of precise definition of healthy, ageing and degenerated discs. Decreased nutrition is the final common pathway for DDD and the status of the endplate (EP) plays a crucial role in controlling the extent of diffusion, which is the only source of nutrition. The vascular channels in the subchondral plate have muscarinic receptors but the possibility of enhancing diffusion pharmacologically by dilation of these vessels has not been probed. Although it is well accepted that EP damage will affect diffusion and thereby nutrition, there is no described method to quantify the extent of EP damage. Precise definitions with an objective method of differentiating healthy, ageing and degenerated discs on the basis of anatomical integrity of the disc and physiological basis of altered nutrition will be useful. This information is an urgent necessity for better understanding of DDD and also strategizing prevention and treatment. Seven hundred and thirty endplates of 365 lumbar discs from 73 individuals (26 healthy volunteers and 47 patients) with age ranging from 10-64 years were evaluated by pre-contrast and 10 min, 2, 4, 6 and 12 h post contrast MRI after IV injection of 0.3 mmol/kg of Gadodiamide. End plates were classified according to the extent of damage into six grades and an incremental score was given for each category. A total endplate score (TEPS) was derived by adding the EP score of the two endplates for each concerned disc. The base line value (SI(base)) and the signal intensity at particular time periods were used to derive the enhancement percentage for each time period (Enhancement (%) = SI(tp) - SI(base)/SI(base) x 100). The enhancement percentage for each time period, the time for peak enhancement (T-max) and the time intensity curve (TIC) over 12 h were used to study and compare the diffusion characteristics. The differences in pattern of diffusion were obvious visually at 4 h which was categorized into five patterns-Pattern A representing normal diffusion to Pattern E representing a total abnormality in diffusion. Degeneration was classified according to Pfirrmann's grading and this was correlated to the TEPS and the alterations in diffusion patterns. The relationship of TEPS on the increase in DDD was evaluated by a logistic curve and the cut point for severe DDD was found by ROC curve. The influence of the variables of age, level, Modic changes, instability, annulus fibrosis defect (DEBIT), TEPS and diffusion patterns on DDD was analyzed by multiple and stepwise regression analysis. Oral nimodipine study: Additional forty lumbar end-plates from four young healthy volunteers were studied to document the effect of oral nimodipine. Pre-drug diffusion levels were studied by pre and post contrast MRI (0.3 mmol/kg of gadodiamide) at 10 min, 2, 4, 6, 12 and 24 h. Oral nimodipine was administered (30 mg QID) for 5 days and post-contrast MRI studies were performed similarly. Enhancement was calculated at vert...

“…(Yan, Ding, Liu, 1993;Lian-Quing, Heng-Shan, Gang, 1993;Dollery, 1999;Blardi et al, 2002;Qiu et al, 2004;Zhonggui et al, 2004;Hernandez-Hernandez et al, 2002). Previous studies showed these data, but sampling was concluded between 5 and 10h after dosing, thereby possibly missing a longer elimination phase.…”

Section: Pharmacokinetic Studymentioning

confidence: 99%

Determination of nimodipine in plasma by HPLC-MS/MS and pharmacokinetic application

Nascimento

Moraes

Bezerra

et al. 2010

Braz. J. Pharm. Sci.

To develop and validate a rapid, specific and highly sensitive method to quantify nimodipine in human plasma using dibucaine as the internal standard (IS). The analyte and IS were extracted from plasma samples by liquid-liquid extraction using hexane-ethyl acetate (1:1 v/v). The chromatographic separation was performed on a Varian ® Polaris C18 analytical column (3 mm, 50 x 2.0 mm) and pre-column Securityguard TM C18 (4.0 x 3.0 mm) with a mobile phase of Acetonitrile-Ammonium acetate 0.02 ml/L (80:20v/v). The method had a chromatographic run time of 4.5 min and linear calibration curve over the range of 0.1-40 ng/mL (r > 0.9938). The limit of quantification was 100 pg/mL. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. This validated method was successfully applied in determining the pharmacokinetic profile of nimodipine tablets of 30 mg administered to 24 healthy volunteers. The proposed method of analysis provided a sensitive and specific assay for nimodipine determination in human plasma. The time for the determination of one plasma sample was 4.5 min. This method is suitable for the analysis of nimodipine in human plasma samples collected for pharmacokinetic, bioavailability or bioequivalence studies in humans.Uniterms: Nimodipine/determination in plasma. Nimodipine/pharmacokinetic profile. Nimodipine/ quantitative analysis. Pharmacokinetics/method validation.Um método rápido, específico e sensível para quantificar nimodipino em plasma humano usando dibucaína como padrão interno (IS) é descrito. O analito e o IS foram extraídos das amostras de plasma por extração líquido-líquido usando hexano-acetato de etila (1:1 v/v). A separação cromatográfica foi realizada utilizando-se uma coluna analítica C18 Varian ® Polaris (3 mm, 50 x 2,0 mm) e uma pré-coluna Securityguard TM C18 (4,0 x 3,0 mm) e acetonitrila-acetato de amônia 0,02 mol/L (80:20 v/v) como fase móvel. O método apresentou tempo total de corrida de 4,5 min e curva de calibração linear com concentrações entre 0,1-40 ng/mL (r > 0,9938). O limite de quantificação foi de 100 pg/mL. Os valores de precisão e exatidão foram obtidos por meio da análise das amostras de controle de qualidade. A análise de uma única amostra de plasma foi realizada em 4,5 minutos. A metodologia validada foi aplicada na determinação do perfil farmacocinético do nimodipino, comprimido de 30 mg administrado em 24 voluntários saudáveis. O método para quantificar nimodipino em plasma é adequado para aplicação em estudos farmacocinéticos, biodisponibilidade e bioequivalência em humanos.