Bioequivalence and Bioavailability Forum • Difficult formulations

Difficult formulations [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2014-11-19 21:15 (4232 d 18:04 ago) – Posting: # 13891
Views: 16,053

Hi Angus,

❝ […] it shows the variability at the earlier time intervals in the fed state is huge and that makes the point very well. I am thinking that the food delays gastric emptying so the formulations are retained in the stomach ~ 3 hours prior to transiting to the small intestine.

Exactly. That’s actually the idea behind formulations with differently coated pellets.

❝ {would have thought that Concerta would be OK, since it has an IR overcoat component}.

Concerta shows a smaller food effect, but we see some shift in osmotic pumps as well.

❝ I wonder how the within subject variability in the fasted state compares with the fed state for such formulations at the corresponding time intervals.

That’s a difficult question. There are formulations with different release mechanisms on the market. All show a food effect (practically only on rate metrics), some don’t work in fasted state very well (dose dumping), most fail in vitro alcohol-induced dose dumping, variability of the early phase in fed state might be higher (most formulations) or lower (some drugs)… :blahblah:

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Complete thread:

Draft FDA guidance on Methylphenidate Hydrochloride kumarnaidu 2014-11-10 08:16 [Regulatives / Guidelines]
- Five PK metrics + S×F interaction Helmut 2014-11-10 13:57
  - Five PK metrics + S×F interaction AngusMcLean 2014-11-11 19:26
    - Phoenix Helmut 2014-11-11 21:05
      - Phoenix AngusMcLean 2014-11-12 19:25
      - Phoenix AngusMcLean 2014-11-21 00:28
  - Five PK metrics + S×F interaction jag009 2014-11-16 03:39
    - Acceptance limit for the upper 95% confidence bound? Helmut 2014-11-17 12:49
      - Acceptance limit for the upper 95% confidence bound? jag009 2014-11-17 17:29
        
        Quoting László Helmut 2014-11-18 03:56
      - Acceptance limit for the upper 95% confidence bound? AngusMcLean 2014-11-19 13:28
  - Five PK metrics + S×F interaction kumarnaidu 2014-12-09 08:36
    - No RSABE Helmut 2014-12-09 13:18
      - No RSABE kumarnaidu 2014-12-09 14:19
        
        No RSABE Helmut 2014-12-09 14:50
- Five PK metrics + S×F interaction drgunasakaran1 2014-11-10 18:29
  - Five PK metrics + S×F interaction jag009 2014-11-11 18:04
  - Five PK metrics + S×F interaction AngusMcLean 2014-11-11 19:22
    - Five PK metrics + S×F interaction jag009 2014-11-11 20:08
      - Tada! jag009 2014-11-13 20:17
        
        Tada! AngusMcLean 2014-11-13 23:06
        
        Tada! nobody 2014-11-19 09:30
        
        Tada! AngusMcLean 2014-11-19 13:42
        
        Tada! nobody 2014-11-19 13:55
        
        ABEL Helmut 2014-11-19 15:44
        
        ABEL nobody 2014-11-19 16:05
        
        ABEL Helmut 2014-11-19 16:59
        
        ABEL nobody 2014-11-19 17:10
        
        ABEL Helmut 2014-11-19 17:16
        
        ABEL AngusMcLean 2014-11-19 17:45
        
        Difficult formulationsHelmut 2014-11-19 20:15
        
        Difficult formulations nobody 2014-11-19 21:04
        
        Difficult formulations Helmut 2014-11-19 21:49