INVIVO INVITRO CORRELATIONSHIP - PART I

Therapeutic efficacy of pharmaceutical formulation is governed by factor related to both in vivo bioavailability & in vitro dissolution characteristics.

The dissolution rate of a specific dosage form is essentially an arbitrary parameter, which dependent on dissolution medium, agitation, speed etc. These all factor can modify the dissolution characteristic dramatically, so that bioavailability implication of dissolution should be proved through carefully designed IVIVC studies.

According to USP, IVIVC is a rational relationship between a biological property produced by a dosage form and a physiochemical property of same dosage form. The biological properties are Cmax, AUC etc. The physiochemical properties are % drug release under a given condition.

According to FDA, A predictive mathematical model describing the relationship between in vitro property and a relevant in vivo response. The goal of an IVIVC study is to define a relationship between two parameters.

Now, in today’s world of pharmacy pharmaceutical companies rely heavily on invitro dissolution or release test to develop extended release or controlled release dosage forms and ensure their performance in vivo. In 1971 Wagner had already stated that “future research in dissolution rate should be directed mainly towards establishing correlation of invitro data with in vivo data.”

The correlation between in vitro in vivo data is the tool for development and production control. it is also important that the scientific community reach a consensus about what it means by IVIVC.

Generally IVIVC is established when in vitro dissolution is the rate limiting step like Extended release (ER) or Modified release (MR) or Controlled release products means drug should be release in controlled manner so as to maintain constant blood levels for longer period of time.

For this,
1. Begin with suggested or candidate dissolution specifications. Use the IVIVC model to prediction the plasma conc. Time profile of batches whole in vitro dissolution as a function of time in terms of small no of parameter.

2.The model the relationship between this parameter & the in vivo bio equivalence matrix (Cmax,AUC). IVIVC is model readily defined for controlled release dosage form, as compare to immediate release drug because release is rate-limiting step in the absorption process.

IVIVC studies have to be conducted during the early stage of product developments in order to select the most effective formulation and to establish the proper dosage regime.