Abstract
Background: Enteric microencapsulation of the potential immunosuppressant TRAM-34 was investigated as a means of enhancing oral drug delivery and minimizing or eliminating hydrolysis of pyrazole-substituted triarylmethane to the respective alcohol. Method: TRAM-34 was successfully enteric microencapsulated by a coacervation method using the pH-sensitive Eudragit L 100 polymer. In this study, we utilized watermiscible organic solvents such as acetone and ethanol, which are considered safe class 3 solvents according to the ICH guideline. We deemed such an approach suitable for safe scale up and for enteric coating application to other compounds of a similar lipophilicity. Results: The resulting microparticles were spherical and uniform with an average particle size of 460 μm at 15 theoretical loading. The encapsulation efficiency was 90 ± 1.9 and the percentage yield was found to be 91.5 ± 0.3. The oral administration in rhesus macaques of TRAM-34-loaded enteric-coated microparticles illustrated six times enhancement in its oral bioavailability. However, the TRAM-34 plasma concentration was less than the therapeutic effective level. Conclusion: The low oral bioavailability, even after enteric coating, could be attributed to the compound's inherent absorption characteristics and high lipophilicity.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 563-569 |
| Number of pages | 7 |
| Journal | Drug Development and Industrial Pharmacy |
| Volume | 36 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2010 |
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Keywords
- Bioavailability
- Coacervation
- Enteric coating
- Microencapsulation
- Oral
- TRAM-34
ASJC Scopus subject areas
- Drug Discovery
- Pharmacology
- Organic Chemistry
Cite this
Formulation-based approach to support early drug discovery and development efforts : A case study with enteric microencapsulation dosage form development for a triarylmethane derivative TRAM-34; a novel potential immunosuppressant. / Al-Ghananeem, Abeer M.; Abbassi, Maggie; Shrestha, Srishti; Raman, Girija; Wulff, Heike; Pereira, Lara; Ansari, Aftab.
In: Drug Development and Industrial Pharmacy, Vol. 36, No. 5, 05.2010, p. 563-569.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Formulation-based approach to support early drug discovery and development efforts
T2 - A case study with enteric microencapsulation dosage form development for a triarylmethane derivative TRAM-34; a novel potential immunosuppressant
AU - Al-Ghananeem, Abeer M.
AU - Abbassi, Maggie
AU - Shrestha, Srishti
AU - Raman, Girija
AU - Wulff, Heike
AU - Pereira, Lara
AU - Ansari, Aftab
PY - 2010/5
Y1 - 2010/5
N2 - Background: Enteric microencapsulation of the potential immunosuppressant TRAM-34 was investigated as a means of enhancing oral drug delivery and minimizing or eliminating hydrolysis of pyrazole-substituted triarylmethane to the respective alcohol. Method: TRAM-34 was successfully enteric microencapsulated by a coacervation method using the pH-sensitive Eudragit L 100 polymer. In this study, we utilized watermiscible organic solvents such as acetone and ethanol, which are considered safe class 3 solvents according to the ICH guideline. We deemed such an approach suitable for safe scale up and for enteric coating application to other compounds of a similar lipophilicity. Results: The resulting microparticles were spherical and uniform with an average particle size of 460 μm at 15 theoretical loading. The encapsulation efficiency was 90 ± 1.9 and the percentage yield was found to be 91.5 ± 0.3. The oral administration in rhesus macaques of TRAM-34-loaded enteric-coated microparticles illustrated six times enhancement in its oral bioavailability. However, the TRAM-34 plasma concentration was less than the therapeutic effective level. Conclusion: The low oral bioavailability, even after enteric coating, could be attributed to the compound's inherent absorption characteristics and high lipophilicity.
AB - Background: Enteric microencapsulation of the potential immunosuppressant TRAM-34 was investigated as a means of enhancing oral drug delivery and minimizing or eliminating hydrolysis of pyrazole-substituted triarylmethane to the respective alcohol. Method: TRAM-34 was successfully enteric microencapsulated by a coacervation method using the pH-sensitive Eudragit L 100 polymer. In this study, we utilized watermiscible organic solvents such as acetone and ethanol, which are considered safe class 3 solvents according to the ICH guideline. We deemed such an approach suitable for safe scale up and for enteric coating application to other compounds of a similar lipophilicity. Results: The resulting microparticles were spherical and uniform with an average particle size of 460 μm at 15 theoretical loading. The encapsulation efficiency was 90 ± 1.9 and the percentage yield was found to be 91.5 ± 0.3. The oral administration in rhesus macaques of TRAM-34-loaded enteric-coated microparticles illustrated six times enhancement in its oral bioavailability. However, the TRAM-34 plasma concentration was less than the therapeutic effective level. Conclusion: The low oral bioavailability, even after enteric coating, could be attributed to the compound's inherent absorption characteristics and high lipophilicity.
KW - Bioavailability
KW - Coacervation
KW - Enteric coating
KW - Microencapsulation
KW - Oral
KW - TRAM-34
UR - http://www.scopus.com/inward/record.url?scp=77952611039&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952611039&partnerID=8YFLogxK
U2 - 10.3109/03639040903329554
DO - 10.3109/03639040903329554
M3 - Article
C2 - 19929567
AN - SCOPUS:77952611039
VL - 36
SP - 563
EP - 569
JO - Drug Development and Industrial Pharmacy
JF - Drug Development and Industrial Pharmacy
SN - 0363-9045
IS - 5
ER -