The dissolutionīehavior of carvedilol was consistent with the solubility results, where carvedilol release was complete Range 1.2–5.0) and low solubility at high pH (5.8–51.9 μg/mL within the pH range 6.5–7.8). The study revealed that carvedilol exhibited a typical weakīase pH-dependent solubility profile with a high solubility at low pH (545.1–2591.4 μg/mL within the pH Strength, buffer capacity, and buffer species of the dissolution media on the solubility and dissolution behavior
Intestinal fluids and cover the physiological pH range of the GI from 1.2 to 7.8.
Solubility and in vitro dissolution studies was carried out using media that simulate the gastric and Weakly basic Biopharmaceutical Classification Systems (BCS) class II drugs, characterized by low solubilityĪnd high permeability, using carvedilol, a weak base with a pKa value of 7.8, as a model drug. The objective of this study was to investigate the pH-dependent solubility and dissolution of Received accepted 7 July 2015 published online 23 July 2015Ībstract. Rania Hamed,1,4 Areeg Awadallah,1 Suhair Sunoqrot,1 Ola Tarawneh,1 Sami Nazzal,2 Tamadur AlBaraghthi,1 PH-Dependent Solubility and Dissolution Behavior of Carvedilol-Case Example Xem và tải ngay bản đầy đủ của tài liệu tại đây (337.27 KB, 9 trang )ĪAPS PharmSciTech, Vol. All rights reserved.Bạn đang xem bản rút gọn của tài liệu.
#Example bcs class 4 drugs trial#
However, due to lack of understanding of the basic physical chemistry behind these strategies formulation development is still driven by trial and error.īioavailability Dissolution rate Enhanced permeation P-gp efflux.Ĭopyright © 2017 Elsevier B.V.
#Example bcs class 4 drugs series#
Today, the pharmaceutical industry has as its disposal a series of reliable and scalable formulation strategies for BCS Class IV drugs. It also brings to forefront the current lack of regulatory guidelines which poses difficulties during preclinical and clinical testing for submission of NDA and subsequent marketing. The review also focuses on the roadblocks in the clinical development of the aforementioned strategies such as problems in scale up, manufacturing under cGMP guidelines, appropriate quality control tests, validation of various processes and variable therein etc. Some of the techniques employed are lipid based delivery systems, polymer based nanocarriers, crystal engineering (nanocrystals and co-crystals), liquisolid technology, self-emulsifying solid dispersions and miscellaneous techniques addressing the P-gp efflux problem. This article highlights the various techniques and upcoming strategies which can be employed for the development of highly notorious BCS class IV drugs. Also, ideal systems for BCS class IV should produce a therapeutic concentration of the drug at reasonable dose volumes for intravenous administration. Ideal oral dosage forms should produce both a reasonably high bioavailability and low inter and intra subject variability in absorption. To be clinically effective these drugs require the development of a proper delivery system for both oral and per oral delivery.
The importance of the formulation composition and design to successful drug development is especially illustrated by the BCS class IV case. The inherent hurdles posed by these drugs hamper their translation to actual market. Formulation and development of an efficacious delivery system for BCS class IV drugs are herculean tasks for any formulator. A decade back, extreme examples of class IV compounds were an exception rather than the rule, yet today many drug candidates under development pipeline fall into this category. Also, most of the class IV drugs are substrate for P-glycoprotein (low permeability) and substrate for CYP3A4 (extensive pre systemic metabolism) which further potentiates the problem of poor therapeutic potential of these drugs. Some of the problems associated include low aqueous solubility, poor permeability, erratic and poor absorption, inter and intra subject variability and significant positive food effect which leads to low and variable bioavailability. BCS class IV drugs (e.g., amphotericin B, furosemide, acetazolamide, ritonavir, paclitaxel) exhibit many characteristics that are problematic for effective oral and per oral delivery.
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