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I am into formulation-kinetics area where my job is to carryout
pharmacokinetic evaluation of novel formulations. Presently, I am
working on pharmacokinetic evaluation of nasal hydrogels. One of the
first steps in conducting pharmacokinetic studies for novel formulation
is the appropriate dose selection in suitable animal model.
Following cases are presented:
Case 1: Oral human dose of the drug used : 180 mg/day (BCS Class II
drug); Solubility in water: 2 mcg/mL
Case 2: Oral human dose of the drug used : 1 mg/day (BCS Class III
drug); Solubility in water: 100 mg/mL
Since the animal model chosen is rabbit, the maximum volume that can be
administered into rabbit nostril is 75 microliter.
The reported maximum volume for administration through nasal route in
humans is 150 microliter.
1. What would be the appropriate dose for PK study in both the cases
(case 1 & 2) in rabbits ?
2. Should allometric considerations be made while evaluating such novel
formulations of known drugs?
3. If allometric considerations are made, the drug concentration in
nasal gel (in case 1) may be supported in rabbits (due to low drug
content) but when the same is extrapolated in humans (where maximum
nasal volume that can be administered is 150 microliter, the small
quantity of formulation may not support high dose required for humans)
the study is not feasible.
Note: Since in case I, we have BCS II drug, poor solubility of drug
limits the drug strength in the formulation which is a hydrogel.
BITS-Pilani, Hyderabad Campus,
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The following message was posted to: PharmPK
I would like to draw your attention to a factor that could prove to be
important. Since you are considering an intranasal hydrogel, I am
assuming it would have significant residence time in the nose. This could result
in substantial amount of direct nose to brain delivery and have a much
higher large brain concentration as compared to oral doses where this
phenomenon is absent.
Siladitya Ray Chaudhuri, PhD
Senior Scientist II
Simulation Technologies (GastroPlus)
Simulations Plus, Inc.
42505 10th Street W.
Lancaster, CA 93534, USA
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