A Technique to Estimate In Vivo Dissolution Profiles Without Data from a Solution

Abstract

Abstract. Dissolution tests are expected to ensure adequate in vivo product performance. Given the recent progress in the ability to predict of human permeability, it is possible to synthesize the plasma drug concentration-time profile from human permeability predictions and the results of the first-in-human trial and use these data to synthesize a pharmacokinetic profile for a solution and provide an initial estimate of the in vivo dissolution profile. This manuscript provides details of such a deconvolution methodology in order to provide an initial estimate of in vivo dissolution. Plasma metoprolol concentration-time data from a previously published study examining the pharmacokinetics of three metoprolol formulations (100 mg), slow, moderate, and fast releasing, and an oral solution (50 mg) were used to estimate in vitro dissolution profiles. A one-compartment unit impulse function was used, and the absorption rate was estimated from animal permeability data (synthetic solution method). The results were compared to those obtained using a unit impulse function estimated from the oral solution data. In vivo dissolution profiles estimated from animal permeability data were similar to those estimated from the oral solution data. Ratios of absorption rate constants (synthetic solution method/oral solution) ranged from 1 to 1.3. The synthetic solution method offers a way to estimate in vivo dissolution profile through deconvolution. It is applicable in cases where it is not possible or feasible to obtain data from a solution. It performs best in cases where dissolution is the rate-limiting step in the absorption process.

The Biopharmaceutics Risk Assessment Roadmap for Optimizing Clinical Drug Product Performance

“…Some examples of marketed drug products that would fit in Scenario 1 are listed in Table (Refs. ) and publications that can further illustrate the general related approaches and considerations are also provided as references …”

“…Some examples for this scenario are also in Table (Refs. ) and additional pertinent references are provided as examples for methodology and applications …”

“…Sources of critical knowledge may be from clinical and nonclinical studies including drug substance and dosage form characterization, predictive in vitro systems, isolated tissues, and organ systems. As in some of the referenced articles, modeling and simulation techniques are widely used for targeted data collection, interpretation of data, and prediction of likely outcomes . In addition, techniques such as physiologically based PK modeling (PBPK) can incorporate early information related to the drug substance characteristics and its in vitro and in vivo performance.…”

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Research Paper Review: A Technique to Estimate In Vivo Dissolution Profiles Without Data from a Solution

“…ack Cook from Pfizer recently published a research paper in The AAPS Journal (1). The topic of the paper was a starting point for developing a dissolution in vitro method using a profile generated by deconvolution of a synthesized in vivo profile.…”