Sari P.,Ministry of Health |
Sun J.,China Pharmaceutical University |
Razzak M.,Pharmaceutical Consultant |
Tucker I.G.,University of Otago
AAPS PharmSciTech | Year: 2016
A combination of lipophilic and hydrophilic drugs in a single solution is a challenge due to their different physicochemical properties. In vitro and in vivo release studies are useful to optimize this solution. The in vitro (Franz diffusion cell) release rate of levamisole phosphate from an isotropic vehicle of medium chain mono and diglycerides (MCMDG) was significantly slower than the release from water. The injectable solution of the isotropic MCMDG-based system was prepared with 13.65% of levamisole phosphate and 0.5% of abamectin. Two milliliters/50 kg (0.04 ml/kg) was injected subcutaneously into five healthy adult sheep. None of the animals showed the signs of inflammation at injection site. Both drugs were assayed using validated HPLC methods. The absorption rates for levamisole (0.71 ± 0.32 h−1) and abamectin (0.24 ± 0.08 day−1) from the MCMDG-based formulation were considerably slower than those of other studies conducted on the commercial products. The tmax was delayed for levamisole (2.20 ± 0.45 h) and abamectin (4.20 ± 1.64 days) compared with those in published studies. Longer MRT values for levamisole (6.14 ± 1.14 h) and abamectin (8.80 ± 1.39 days) were found in this study compared to those reported. A correlation was observed between in vivo fraction absorbed and in vitro fraction released for levamisole phosphate in the MCMDG-based formulation. The injection vehicle of isotropic MCMDG-based system delayed the subcutaneous absorption of levamisole phosphate and abamectin compared to the commercial subcutaneous injection products for levamisole and abamectin. Notably, this isotropic MCMDG-based vehicle system is prepared with a combination of two drugs with different physicochemical properties. © 2016 American Association of Pharmaceutical Scientists
Stegemann S.,Capsugel |
Klebovich I.,Semmelweis University |
Antal I.,Semmelweis University |
Blume H.H.,SocraTec RandD Ltd. |
And 7 more authors.
European Journal of Pharmaceutical Sciences | Year: 2011
With a New Drug Application (NDA) innovative drug therapies are reaching the market in a specific dosage form for one or more clinically proven indications of which after expiration of the patent or the data exclusivity copies are launched using Abbreviated New Drug Applications (ANDA). Advanced therapies that emerged from launched molecules during their product life-cycle have gained considerable attention as clinical practice provides evidence for additional therapeutic values, patient centric delivery systems show improved therapeutic outcomes or emerging technologies offer efficiency gains in manufacturing or access to emerging markets. The USA and European regulatory framework has set reasonable regulations in place for these " Supergenerics" or "hybrid" applications. While these regulations are relatively recent the pharmaceutical industry is just starting to use this route for their product development and life-cycle management. From a clinical perspective the potential for advanced product development have been demonstrated. Yet, there is still a lag of common understanding between the different stakeholders regarding the development, application process and commercial incentive in developing enhanced therapeutic entities based on existing drug products for the market. © 2011 Elsevier B.V. All rights reserved.
Shah R.R.,Pharmaceutical Consultant
Drug Safety | Year: 2017
Reversible posterior leukoencephalopathy syndrome (RPLS), also known frequently as posterior reversible encephalopathy syndrome (PRES), is a characteristic acute neuro-radiology syndrome with clinical presentation that typically includes acute hypertension, seizures and other neurological symptoms and signs. Many patients with RPLS have (a history of) pre-existing hypertension and in receipt of diuretics. It is being diagnosed more frequently and in association with an increasing number of morbidities and medications. Drugs most frequently implicated are immunosuppressant drugs and anticancer agents, including a number of anti-angiogenic tyrosine kinase inhibitors (TKIs). Hypomagnesaemia is a frequent finding at presentation in RPLS patients, which is known to lead to or aggravate hypertension. Pre-eclampsia, a variant of RPLS, responds effectively to intravenous magnesium. Cyclosporin, tacrolimus and some TKIs that induce RPLS are also known to give rise to both hypertension and hypomagnesaemia. This raises an interesting hypothesis that hypomagnesaemia may play a contributory role in triggering RPLS in some patients by acutely raising the blood pressure further. Additional systematic studies are required to test this hypothesis. If the hypothesis is confirmed, hypomagnesaemia offers an effective target for risk mitigation and prevention of RPLS in patients identified at risk. © 2017 Springer International Publishing Switzerland
Shah V.P.,Pharmaceutical Consultant |
Bansal S.,Hoffmann-La Roche
Bioanalysis | Year: 2011
Bioanalytical methods employed for the quantitative determination of drugs and their metabolites in biological fluids provide essential regulatory data for bioavailability, bioequivalence, pharmacokinetic and toxicokinetic studies. The quality of these studies is directly related to the underlying bioanalytical data. Data generated by a typical bioanalytical laboratory is submitted to not only the local regulatory agency, but also to multiple regulatory agencies worldwide. Many pharmaceutical companies and CROs are now performing bioanalytical work for global submissions and the regulatory agencies are often reviewing the bioanalytical work performed in other countries. The bioanalytical workplace has become global and therefore needs universal rules for quality and compliance of bioanalysis. This paper provides a historical perspective and insight into the development and evolution of the regulatory guidance for bioanalytical method validation and analysis of samples. © 2011 Future Science Ltd.
PubMed | Lonza AG, University Utrecht, Pharmaceutical Consultant, China Pharma and 9 more.
Type: Journal Article | Journal: Journal of pharmaceutical sciences | Year: 2016
The chairs of each of the 8 Special Interest Groups of the Board of Pharmaceutical Sciences of the International Pharmaceutical Federation have compiled opinions with regard to major challenges for the pharmaceutical sciences over the next 5-10 years. Areas covered are drug design and discovery, natural products, formulation design and pharmaceutical technology, pharmacokinetics/pharmacodynamics and systems pharmacology, translational and personalized medicine, biotechnology, analytical sciences and quality control, and regulatory science.
News Article | November 15, 2016
Led by well-known Pharmaceutical Consultant Andrew Campbell, ComplianceOnline’s popular seminar on quality oversight of CMOs comes to Florida in 2017. This training program will address regulatory requirements for CMO quality oversight and will help attendees understand the CMO business model. Given the constant updates in the industry, each session in the seminar will cover these industry updates and focus on best practices on how to manage CMOs on an ongoing basis. The training will focus on the topics such as selection and qualification of CMOs, development of quality agreements, understand CMO operations, and review of key CMO records and others. Seminar instructor Andrew Campbell has over 25 years of pharmaceutical quality assurance and quality systems experience in both industry and consulting roles. Mr. Campbell has worked in clinical supply and commercial manufacturing environments, and has experience with integrated manufacturing and contract manufacturing business models. He has extensive expertise in the areas of deviation - CAPA, change control, GMP auditing, GMP training, and regulatory inspection preparation and management. For more information or to register for the seminar, please click here. Dates: Thursday, March 30, 2017 (8.00 AM- 4.30 PM) and Friday, March 31, 2017 (9.00 AM- 1.00 PM) Location: Tampa, FL Registration Cost: $1,899.00 per registration Early bird discounts: For discounts on early registrations, please click here. Register by phone: Please call our customer service specialists at +1-888-717-2436 or email to customercare(at)complianceonline(dot)com For more information on ComplianceOnline or to browse through our trainings, please visit our website. ComplianceOnline is a leading provider of regulatory compliance trainings for companies and professionals in regulated industries. ComplianceOnline has successfully trained over 35,000 professionals from 9,000 companies to comply with the requirements of regulatory agencies. ComplianceOnline is headquartered in Palo Alto, California and can be reached at http://www.complianceonline.com. ComplianceOnline is a MetricStream portal. MetricStream (http://www.metricstream.com) is a market leader in Enterprise-wide Governance, Risk, Compliance (GRC) and Quality Management Solutions for global corporations. For more information please contact:
PubMed | DOLE Pharma LLC, Pharmaceutical Consultant, Carol Davila University of Medicine and Pharmacy and University College London
Type: Journal Article | Journal: International journal of pharmaceutics | Year: 2015
The Biopharmaceutics Classification System (BCS) for oral immediate release solid drug products has been very successful; its implementation in drug industry and regulatory approval has shown significant progress. This has been the case primarily because BCS was developed using sound scientific judgment. Following the success of BCS, we have considered the topical drug products for similar classification system based on sound scientific principles. In USA, most of the generic topical drug products have qualitatively (Q1) and quantitatively (Q2) same excipients as the reference listed drug (RLD). The applications of in vitro release (IVR) and in vitro characterization are considered for a range of dosage forms (suspensions, creams, ointments and gels) of differing strengths. We advance a Topical Drug Classification System (TCS) based on a consideration of Q1, Q2 as well as the arrangement of matter and microstructure of topical formulations (Q3). Four distinct classes are presented for the various scenarios that may arise and depending on whether biowaiver can be granted or not.
Crommelin D.J.A.,University Utrecht |
De Vlieger J.S.B.,A.P.Pharma |
Weinstein V.,Teva Pharmaceutical Industries |
Muhlebach S.,A.P.Pharma |
And 2 more authors.
AAPS Journal | Year: 2014
In the last decade, discussions on the development of the regulatory framework of generic versions of complex drugs such as biologicals and non-biological complex drugs have attracted broad attention. The terminology used is far from harmonized and can lead to multiple interpretations of legal texts, reflection papers, and guidance documents regarding market introduction as well as reimbursement. This article describes the meaning of relevant terms in different global regions (Europe, USA, WHO) and offers a proposal for a globally accepted terminology regarding (non-) biological complex drugs. © 2013 American Association of Pharmaceutical Scientists.
PubMed | DOLE Pharma LLC, Pharmaceutical Consultant and Carol Davila University of Medicine and Pharmacy
Type: Journal Article | Journal: International journal of pharmaceutics | Year: 2016
Both biopharmaceutics classification system (BCS) and topical drug classification system (TCS) are based on sound scientific principles with the aim of providing biowaiver and reducing regulatory burden without lowering the quality requirements and standards of approval for the drug products. BCS is based on the solubility and permeability properties of the active pharmaceutical ingredient (API, or drug substance) whereas the TCS is based on the qualitative and quantitative composition of the dosage form and the in vitro release rate of the active ingredient as key decision tools. Both BCS and TCS take drug release and dissolution as their guiding principle for providing biowaiver, increasing the availability and affordability of safe and effective medicines to the consumers and at the same time maintaining the drug product quality.
Shah R.R.,Pharmaceutical Consultant
Drug Safety | Year: 2016
Since the approval of the first molecularly targeted tyrosine kinase inhibitor (TKI), imatinib, in 2001, TKIs have heralded a new era in the treatment of many cancers. Among their innumerable adverse effects, interstitial lung disease (ILD) is one of the most serious, presenting most frequently with dyspnea, cough, fever, and hypoxemia, and often treated with steroids. Of the 28 currently approved TKIs, 16 (57 %) are reported to induce ILD with varying frequency and/or severity. The interval from drug administration to onset of ILD varies between patients and between TKIs, with no predictable time course. Its incidence is variously reported to be approximately 1.6–4.3 % in Japanese populations and 0.3–1.0 % in non-Japanese populations. The mortality rate is in the range of 20–50 %. Available evidence (primarily following the use of erlotinib and gefitinib in Japan because of the unique susceptibility of that population) has identified a number of susceptibility and prognostic risk factors (male sex, a history of smoking, and pre-existing pulmonary fibrosis being the main ones). Although the precise mechanism is not understood, collective evidence suggests that immune factors may be involved. If TKI-induced ILD is confirmed by thorough evaluation of the patient and exclusion of other causes, management is supportive, and includes discontinuation of the culprit TKI and administration of steroids. Discontinuing the culprit TKI presents a clinical dilemma because the diagnosis of TKI-induced ILD in a patient with pre-existing pulmonary fibrosis can be challenging, the patient may have TKI-responsive cancer with no suitable alternative, and switching to an alternative agent, even if available, carries the risk of the patient experiencing other toxic effects. Preliminary evidence suggests that therapy with the culprit TKI may be continued under steroid cover and/or at a reduced dose. However, this approach requires careful individualized risk–benefit analysis and further clinical experience. © 2016 Springer International Publishing Switzerland