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Predicting In Vitro Dissolution of Extended Release Drugs from In Vivo Profiles

Learn how Biopharmetrics successfully predicted in vitro dissolution for extended-release formulations using in vivo profiles of immediate-release drugs.

Case Study: Methodology for Predicting In Vitro Dissolution from In Vivo Profiles

Goals - Aim 1

Build a model based on literature data that:

Validate the model:

Base PK Model & Noncompartmental Analysis of Predictions

Detailed Table of Base PK Model Parameters and Noncompartmental Analysis Predictions
Comparative Table Showing Base PK Model and Noncompartmental Analysis Outcomes

Data extracted from Colburn et al, 1983

Visual Predictive Check of Base Model

Compare Distribution of NCA parameters

Graph illustrating the Visual Predictive Check of the Base Model, showcasing the predicted versus observed data points with confidence intervals.

Goals - Aim 2

Define absorption profiles for drug QD 40 mg that are equivalent to BID 20 mg…

There are two types of formulations to consider:

Graph illustrating sample Hill function profiles with varying parameters.

Sample Hill Function Profiles

Cumulative dissolution function

Sample Double Weibull Profile

There are two types of formulations to consider:

Note: MDT1=MDT2=MDT
b1=b2=b
F1=0.5
Tlag2=4.5
MDT controls length of
pulse and Tlag
controls timing of
second pulse
Graph illustrating the Sample Double Weibull Profile with drug dissolution data
Formula for Sample Double Weibull Profile used in drug dissolution modeling

Simulation of population median response at steady state

Formulation Optimization

Optimal Hill & Double Weibull Profiles

Graph showing the optimal Hill profile for drug release analysis.
Graph depicting the optimal double Weibull profile for drug release study.

Simulated Plasma Profiles & Conclusion

Simulated Plasma Profiles

A QD pulsed delivery strategy appears to achieve highest similarity to the Reference BID regimen.

Who We Are

Pioneering Drug Development: Biopharmetrics Consultancy

At Biopharmetrics, we are dedicated to empowering the pharmaceutical industry through our consultancy services. With a focus on navigating uncertainties in research and regulatory inquiries, we provide expert guidance that fosters confidence in the development of groundbreaking medicines, ultimately enhancing the lives of patients worldwide.

biopharmetric About section

Frequently Asked Question?

Understanding Our Services Through Case Studies

At Biopharmetrics, we employ sophisticated modeling techniques that integrate in vivo data with literature insights to build predictive models. These models not only describe literature data but also incorporate variability in parameter values, allowing simulations of trials of varying sizes and designs. By validating these models against comparator formulations and adjusting formulation parameters as necessary, we ensure accurate predictions of in vitro dissolution from in vivo profiles.

Biopharmetrics employs a range of methodologies tailored to the specific needs of each formulation. For instance, we define absorption profiles for different formulations, such as slow-release matrices and pulsatile release systems, using techniques like Hill functions and double Weibull functions. These models account for factors like dissolution kinetics, manufacturing feasibility, and performance expectations, ensuring that the predicted profiles align with desired clinical outcomes.

At Biopharmetrics, we recognize the importance of addressing variability and optimizing formulations to ensure reliable predictions of drug release kinetics. Through meticulous sensitivity analysis and formulation optimization, we identify and mitigate biases in predictions while maximizing the similarity of simulated plasma profiles to reference regimens. Our approach considers factors like variation in median dissolution time (MDT), pulse timing, and release rates to develop robust formulations that meet both regulatory requirements and therapeutic objectives.

Testimonials

Discover What Our Clients Have to Say

We had an outstanding experience working with Biopharmetrics. Their deep expertise in PBPK Modelling & Simulation was evident from the start of the mAb project. The Clinical Pharmacology consultancy support in clarifying queries from the Regulatory Agency and Principal Investigator of our upcoming trial was helpful. The team’s dedication to our project, attention to detail and strict adherence to our timelines helped us achieve our goals ahead of schedule. They worked closely as part of the regular project team and took utmost care in proposing any solutions. We appreciate their commitment and highly recommend Biopharmetrics for anyone seeking PBPK Services." - Battery Bio at Vial

Vial
Sonam Bhuptani Vice President, USA

We engaged Biopharmetrics for IVIVC services for our products and continue to work with them, they have been very proactive in proposing solutions like optimizing the dissolution profile, selecting bio-relevant dissolution media based on pilot bio results and shortlisting the pilot batches for pivotal BE studies. Their experience in using mathematical modelling tools ie IVIVC and PBPK for predictions has helped us immensely. They have been an integral part of R&D projects, working closely with CFT’s and aligning the deliverables as per our timelines. We recommend Biopharmetrics to others who are experiencing challenges in their formulation R&D

appcure-labs-client-logo
Kishore Manager- Formulations R&D
Appcure Labs, USA& India