PharmPK Discussion - PK study of novel nasal formulation with BCS II drug

• On 5 Feb 2012 at 11:08:40, Rahul Vats (rahulvats1983.-a-.gmail.com) sent the message
  

  
  Dear All,
  
  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.
  
  Questions:
  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.
  
  Regards,
  
  Rahul Vats
  BITS-Pilani, Hyderabad Campus,
  Mobile: 9948921404
  
  

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• On 5 Feb 2012 at 18:01:59, Siladitya Ray Chaudhuri (bourne5321.at.gmail.com) sent the message
  

  
  The following message was posted to: PharmPK
  
  Hi Rahul,
  
  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.
  
  Thanks,
  Ray
  
  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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