Course "Drug dissolution testing and establishing plasma drug levels in humans" has been pre-approved by RAPS as eligible for up to 12 credits towards a participant's RAC recertification upon full completion. Drug dissolution testing is an essential and critical step for appropriate and efficient product development such as tablet and capsule. A number of approaches are used to conduct dissolution testing using different apparatuses and methods. Making a choice for an appropriate apparatus and method has always been confusing and challenging. This seminar will provide relevant pharmacokinetics and physiological background so that making this choice becomes easier and instinctive. No prior knowledge of pharmacokinetic and/or physiology is required; however, these will be explained in very simple terms to help attendees in selecting or developing a dissolution method. This seminar will describe in detail the theoretical aspect of the drug dissolution testing including method development. Pros and cons of different approaches will be explained in detail.
Furthermore, drug dissolution testing is extensively conducted to provide an estimate/prediction of expected drug levels in humans. Commonly, concepts of convolution/deconvolution and in vitro-in vivo correlation (IVIVC) are described in this respect, unfortunately with limited success. Difficulties and limitations of the currently suggested approaches will be highlighted. This seminar will provide details of the underlying scientific principles involved in convolution, deconvolution and IVIVC techniques with simple practical examples. In this regard, a unique and simple approach based on convolution technique using spreadsheet software will be described.
Why you should attend:
Pharmaceutical product developments and assessments require extensive use of in vitro drug dissolution testing and convolution/deconvolution techniques for predicting plasma drug levels. Often such testing are presented in isolation (independent to their physiological link or relevance), however, this seminar will train attendees for developing these techniques using the principles of pharmacokinetics and physiology. The seminar will provide unique opportunity to learn scientifically valid drug dissolution testing and establishing plasma drug levels.
It would be an unmatched opportunity to learn from an internationally recognized leader of the subject. A must attend seminar for anyone involved in product developments and assessments of solid oral dosage forms!
Areas Covered in the Session:
Physiological and Pharmacokinetic Principles:
• Dissolution and related physiological terms: Drug absorption, permeation, relevant GI tract environment.
• Basic and required pharmacokinetic principles including terminologies such as plasma drug concentration-time profiles/curves, rates of absorption and elimination, Cmax, Tmax, half-life, AUC, apparent volume of distribution, bioavailability/bioequivalence, etc.
• Defining, and differentiating, drugs/medicines and drug/medicinal products
• Defining quality of drugs/medicines and drug/medicinal products.
• Generic vs innovator's products (Similarities and differences)
Drug Dissolution Testing:
• What is drug dissolution Testing and Why to conduct such tests?
• Dissolution theory, sink conditions and intrinsic dissolution rate
• Drug Dissolution Testing vs Solubility determination
• Drug Dissolution vs Drug Release Testing - Is there a difference?
• Dissolution Testing Apparatus:
o Rotating basket (USP Apparatus 1)
o Rotating paddle (USP Apparatus 2)
o Reciprocating cylinder (USP Apparatus 3)
o Flow-through cell (USP Apparatus 4)
o Non-compendial (Crescent-shape)
• Setting up a dissolution tester (e.g. Basket and paddle)
• Dissolution equipment qualification (Performance Tablets vs Mechanical Calibration)
• Tolerances and results Interpretation
o Immediate release
o Extended release
o Delayed release
o Current Requirements And Interpretations
• Dissolution Method Developments
o General requirements
o Selection of dissolution medium
o Apparatus and agitation rate
o Sampling (time points & filtration)
o Acceptance criteria (Pharmacopeial, similarity factor (F2), physiologically relevant, etc.)
o QC method, bio/clinical relevant methods
o Discriminatory vs non-discriminatory dissolution methods
o Product dependent vs product independent Methods
o Dissolution method validation vs analytical (quantitation) method validation
o (Specificity, Linearity/range, Accuracy/recovery, Precision, Robustness)
Linking Dissolution Results to Plasma Drug Levels:
• Concepts of convolution, deconvolution and in vitro in vivo correlation (IVIVC), their requirements and (un)suitability for predicting plasma drug levels
• Requirements for appropriate and relevant dissolution results
• Convolution vs deconvolution methods which one to use and why?
• Predicting plasma drug levels (Linking dissolution results to physiology)
• Theoretical background
• Converting dissolution results into plasma drug levels/profiles
• Practical application with step-by-step instructions
• Practical hands-on interactive demonstration of predicting/estimating of plasma drug levels using Excel spreadsheet software. Attendees may use their computers as well to follow the instructions for obtaining plasma drug levels.