Journal of Bioequivalence & Bioavailability最新文献

{"title":"Bioequivalence Guidelines Requirements for Orally Administered Generics (IR Products) in Gulf Cooperation Council Countries, European Union and United States of America","authors":"E. Elangovan","doi":"10.35248/0975-0851.19.11.387","DOIUrl":"https://doi.org/10.35248/0975-0851.19.11.387","url":null,"abstract":"The importance of the bioequivalence requirements is increasing in the GCC (Gulf Cooperation Council) region pertaining towards the growth of generic drug market. GCC bioequivalence guidelines describes the requirements for bioequivalence study as per this region regulatory requirements. This review article mainly focuses on bioequivalence study requirements in the Gulf Cooperation Council countries, European union countries and the United States of America that needs to be fulfilled in order to successfully submit a generic application. This comparison includes the bioequivalence approaches such as study design, sample size, study condition, pharmacokinetic parameters, statistical analysis, narrow therapeutic index drugs, highly variable drug products and BCS based bio waiver requirements. The rationale for this article is to give prompt overview on the bioequivalence requirements in these region and in comparison with well-established regulatory such as USFDA and EMA. In addition, it also highlights the possibilities for harmonization.","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75363710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biopharmaceutics Classification System (BCS) Based Biowaiver Studies of Lenalidomide Capsules (25 mg) – An Alternative to In vivo Bioequivalence Studies for Generic Oncology Drug Products","authors":"AlSwisi Mahmoud, Boujbel Lassaad, Boujbel Mohamed Amine","doi":"10.4172/0975-0851.1000386","DOIUrl":"https://doi.org/10.4172/0975-0851.1000386","url":null,"abstract":"Lenalidomide, commercialized as Revlimid®, is an immunomodulatory drug, approved as a therapy for Multiple Myeloma and deletion 5q Myelodysplastic syndromes. This molecule shows a promising therapeutic potential in other hematologic malignancies. According to the European Medicines Agency (EMA), lenalidomide is considered as a fully absorbed drug substance, however, there is no sufficient data on solubility that enables its BCS classification. Therefore, as per the International Council for Harmonization (ICH) guideline, a solubility study has been done by Les Laboratoires Medis to prove that lenalidomide is a highly soluble compound. This demonstration requires the investigation in different buffer solutions within the range of pH 1- 6.8 (including pKa) at 37 ± 1°C and we have proceeded with a nominal concentration (1.0 mg/ml) which represent ten times the target concentration (0.1 mg/ml). The main reason of conducting this study is to evaluate the possibility of a BCS-based biowaiver for the consent of a generic oncology drug product unescorted by any further in vivo bioequivalence (BE) studies, also, to prove that Lenalidomide can be classified as highly soluble and highly permeable, i.e., BCS class I. The objective of establishing the BCS-based biowaiver procedure is to minimize the need for in vivo BE studies, that would reduce the exposure of healthy volunteers to oncology drugs such as lenalidomide, to prove BE. The test product and Revlimid were evaluated by in vitro methods as stated by ICH guidelines in three dissolution buffers: pH 1.2, 4.5, and 6.8, and QC release medium. The obtained results revealed that both, the test product and Revlimid have exhibited a very rapid dissolution rate (i.e. >85% in 15 min) in all dissolution buffers which infers that the test product complies with the similarity requirements for comparative dissolution testing versus the reference product. It is concluded that lenalidomide 25 mg capsules test product is bioequivalent to reference product using BCS biowaiver.","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"213 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75734041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single Dose Bioequivalence Study of Two Rivaroxaban Tablet Formulations, Administered Orally after Being Crushed and Suspended in Apple Puree","authors":"Simona Nicoleta Duna, Adrian Ghita, Adelina Ciuciuleaca, Irene Manzanera, David Puibert, S. Rizea‐Savu","doi":"10.35248/0975-0851.19.11.388","DOIUrl":"https://doi.org/10.35248/0975-0851.19.11.388","url":null,"abstract":"The bioavailability of an active substance might be altered when a solid oral dosage form (SODF) is crushed or disintegrated and mixed with fluids or food in order to assist swallowing. In consequence, the current European Medicines Agency (EMA) practice is to request comparative bioavailability testing for bridging safety and efficacy data from a formulation administered whole to the same product administered crushed. Specific criteria for waiving in vivo testing of crushed products are available only for BCS Class I and Class III drugs. Since rivaroxaban is a Class II drug which can be administered crushed and mixed with fluids, any generic formulation has to be tested against the originator in this setting. Therefore, an open label, randomized, single dose, two-period, two-sequence, crossover bioequivalence study with administration of rivaroxaban 10 mg crushed tablets suspended in apple puree was conducted in 24 fasting healthy volunteers. Both rivaroxaban treatments were well tolerated by the study subjects. A standardized, dose efficient and fully reproducible protocol for grinding, mixing and administering investigational medicinal products was developed and applied. Assessment of bioequivalence was based on plasma concentrations of parent rivaroxaban, quantified using a validated HPLC/ MS/MS method. The 90% confidence intervals for Cmax and AUC0-t least square mean T/R ratios were within the bioequivalence acceptance range of 80% to 125%. Results from the present study reinforced the bioequivalence conclusion reached for the same test and reference products following administration of whole tablets in fasting state. No notable changes in bioavailability occurred when rivaroxaban tablets were crushed, immediately dispensed in 70 mL apple puree and quantitatively (entire dose recovered) administered to fasting volunteers.","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89453595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Semi-physiologically Based Model for Methylphenidate Pharmacokinetics in Adult Humans","authors":"A. Jackson","doi":"10.35248/0975-0851.19.11.390","DOIUrl":"https://doi.org/10.35248/0975-0851.19.11.390","url":null,"abstract":"To determine if a literature-sourced physiological model for immediate-release (IR) methylphenidate (MPH), with addition of parameters for extended-release (ER) absorption can be adapted for NONMEM analysis to describe extended-release MPH drug products (i.e., Concerta® ER 54 mg tablets and Ritalin-LA® 40 mg capsules) pharmacokinetics (PK) in adults. This semi-physiological model will provide a platform to allow more accurate determination of Cmax in the analysis of methylphenidate plasma data from formulations with complex absorption. Adult reference data for total MPH plasma levels (summation of d- and l- enantiomers) were generated using individual subject parameters from a published NONMEM model for ER MPH (individual subject parameter generated data was used because the true experimental data is proprietary with only the previously-published summary parameters available for public use). The IR physiological model required analysis of both d- and l-MPH enantiomers which were estimated at each time point for the data by calculating the d/l enantiomer ratio from total MPH plasma concentration levels, based upon literature ratio estimates. Absorption was characterized by a fast zero-order and a delayed slow first-order release. Consistent with the literature IR model, two duplicate physiological models were used to describe the d- and l-MPH enantiomers. The mean and variability ratios for the individual subject parameter-generated data/true experimental data were very close to 1.0. The predictive performance of the absorption-modified physiological model and its disposition parameters were demonstrated, as they described both the Concerta® and Ritalin LA® PK and Cmax values very well. The bias was less than 6% for Concerta® peaks while peak 1 for d-Ritalin LA® was 12.9% and peak 2, 7.5%. The IR MPH physiological model, adapted for NONMEM analyses of the ER MPH drug products Concerta® and Ritalin LA® described the individual parameter-generated reference data well for both formulations.","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85591967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biobetters vs. Biosimilars: Opportunities, threats & strategic implications","authors":"G. Bell","doi":"10.4172/0975-0851-c2-035","DOIUrl":"https://doi.org/10.4172/0975-0851-c2-035","url":null,"abstract":"","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"80 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85499986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacists role in helping patients with biosimilars, education, adherence, and appropriate monitoring","authors":"P. Iqbal, Mahmood Ahmadp","doi":"10.4172/0975-0851-C2-036","DOIUrl":"https://doi.org/10.4172/0975-0851-C2-036","url":null,"abstract":"","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"73 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72680029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relative bioavailability of Rolapitant tablets compared with Rolapitant capsules and the effect of food on Rolapitant pharmacokinetics in healthy subjects","authors":"Xiaodong Wang","doi":"10.4172/0975-0851-C1-032","DOIUrl":"https://doi.org/10.4172/0975-0851-C1-032","url":null,"abstract":"","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82023119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heuristic approaches for IVIVC Level A","authors":"Aleks, er Mendyk","doi":"10.4172/0975-0851-C1-033","DOIUrl":"https://doi.org/10.4172/0975-0851-C1-033","url":null,"abstract":"","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"337 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76584518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of Intestinal Absorption Enhancers: Individual vs. Blends with the Carbamoylphosphonate JS403","authors":"Reut Bitton, Marina Tsuriel, R. Suresh, E. Breuer, R. Reich, A. Hoffman","doi":"10.4172/0975-0851.1000372","DOIUrl":"https://doi.org/10.4172/0975-0851.1000372","url":null,"abstract":"JS403 is a carbamoylphosphonate (CPO) molecule that showed anti-metastatic properties in mice. Since JS403 is intended to be a chronic prophylactic drug, the preferred route of administration should be oral. However, it exhibits poor oral bioavailability of less than 1%. The poor intestinal permeability and high solubility implies its classification as BCS class III drug. The aim of this study was to overcome the limited intestinal permeation of JS403 that is regarded as an unmet need in the pharmaceutical industry for this class of drugs. Therefore, the impact of acceptable absorption enhancers on the intestinal permeability of JS403 were examined using established experimental models. The absorption enhancers were: I) sodium caprate (C10), II) sodium deoxycholate (SDC) and III) mono-carboxymethylated chitosan (MCC). The effect of each enhancer was examined alone and also in combinations. In-vitro permeability through enterocytes monolayer was studied using the Caco-2 model, while the oral bioavailability was determined by using the freely moving rat model. The results of this investigation showed that while the use of a single absorption enhancer had no effect on JS403 permeability, the combination of C10 and sodium deoxycholate increased the permeability of JS403 by 10-fold in the in-vitro model. In addition, this blend showed a 2-fold elevation in JS403 oral bioavailability. Both in-vitro and in-vivo results highlight the synergistic potential of the combined enhancers C10 and sodium deoxycholate in enhancing oral bioavailability of BCS class III medications.","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"12 1","pages":"24-28"},"PeriodicalIF":0.0,"publicationDate":"2018-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87952566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analgesic Action by Neuroleptics in Diabetic State","authors":"S. Kashif, S. Naeem, Nausheen Alam Sarosh, M. Khan","doi":"10.4172/0975-0851.1000373","DOIUrl":"https://doi.org/10.4172/0975-0851.1000373","url":null,"abstract":"Purpose: To assess the analgesic role of neuroleptics in hyperglycemic state. \u0000Methods: Amytryptiline and carbamazepine were selected for study. This study was carried out at Pharmacology lab, Institute of Research Pharmaceutical sciences, University of Karachi, and comprised of male and female mice, half of which were made diabetic by giving Alloxan. The objective of this study is to monitor the effects of neuroactive agents on analgesic activity in hyperglycemic mice. \u0000Results: It was observed that Amytryptiline exhibited highly significant analgesic effect in normal as compared to diabetic subjects. It was also observed that both amytryptiline and carbamazepine produce more rapid onset of action and longer duration of action in normal animals when compared with diabetic animals. \u0000Conclusion: The present work on normal and diabetic animals show that both Carbamazepine and Amytryptiline in normal animals produce rapid onset and longer duration of action when compared with diabetic animals.","PeriodicalId":15184,"journal":{"name":"Journal of Bioequivalence & Bioavailability","volume":"110 1","pages":"29-32"},"PeriodicalIF":0.0,"publicationDate":"2018-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87672827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}