**2.9 Steady state studies**

*Pharmaceutical Formulation Design - Recent Practices*

1.The level of significant should be 0.05

ence in primary characteristics to be studied

standardized as much as possible and acceptable.

*2.7.2 Fasting and fed state considerations*

The number of subjects should be sufficient in the study to allow for possible withdrawals or dropouts. In initial study, it is acceptable to replace a subject withdrawal or dropout once it has provided the substituted subject follows the same protocol originally intended for the withdrawn subject and subject is tested under similar conditions. The number of subjects involved in a study is determined by the

2.The error variance associated with the primary characteristics to be studied as

4.The required power, normally >80% to detect the maximum allowable differ-

The studies should be performed on healthy adult volunteers with the aim to minimize variability between the study drugs. Subjects may be males or females; however, the choice of gender should be consistent with usage and safety criteria of the drug. To minimize intra and intersubject variation, the study design should be

Generally, a single dose study should be conducted after an overnight fast (at least 10 hours) and subsequent fasting of 4 hours after administration dosing. For multiple dose studies, 2 hours of fasting before and after the dose are acceptable. Estimation of Cmax and Tmax for the modified release products or drug is given with food in such case fed state studies also been carried out in addition to the normal fasting state bioavailability studies [22]. During fed state studies, the consumption of a high fat breakfast of 950–1000 KCals is required before dosing. The food intake containing at least 50% of these calories must come from fat, 15–20% calories from proteins, and the remaining from carbohydrates. A single standard diet should be followed taking into consideration of all the Indian subcontinent people. The high fat breakfast must be consumed approximately 15 minutes before dosing in fed state

Study conditions such as study environment, diet, fluid intake, post dosing postures, exercise, sampling schedules, etc. are monitored during studies. These conditions are stated in the protocol, and at the end of the study, these should be complied, to assure that all variability factors involved in the study to minimize the products to be tested. Least 48 hours before commencement, the study subjects abstain from smoking, drinking alcohol, xanthine containing foods, coffee, tea and

estimated from a pilot experiment, from previous studies

3.The expected deviation from the reference drug compatible with

**2.7 Selection of the number of subjects**

following considerations:

bioequivalence

*2.7.1 Selection criteria for subjects*

**72**

condition.

**2.8 Study conditions**

beverages, and fruit juices.

Steady state study is considered in the following conditions:

