Abstract
Carvedilol-loaded solid lipid nanoparticles (SLNs) were prepared using solubility parameter (δ) to select the lipid, and hot homogenization to fabricate SLNs. The effect of concentration of Compritol 888 ATO (COMP) and Poloxamer 188 (P-188) on the particle size of blank SLNs was studied using the design of experiments. Further narrow concentration range of COMP and P- 188 was selected and carvedilol-loaded SLNs were prepared to obtain an optimized formulation which was lyophilized (L-SLNs), transformed into enteric compression-coated tablet and evaluated for drug release, X-ray diffraction and cellular uptake mechanism. COMP was chosen as lipid due to its least value of Δδ with carvedilol. The optimized formulation (7.5% COMP, 5.0% P-188 and 1.11% carvedilol) had 161nm particle size and 94.8% entrapment efficiency. The enteric-coated carvedilol-loaded SLNs tablet protected carvedilol from acidic environment and similar prolonged release profiles were obtained from L-SLNs, core tablet and entericcoated tablet. Absence of crystalline carvedilol XRD peak indicated the presence of amorphous carvedilol in SLNs. Higher carvedilol uptake from SLNs compared to drug solution in the Caco-2 cell line exhibited a potential prolonged drug release. Moreover, upon cellular uptake, SLNs could then enter the lymphatic system which will avoid first pass metabolism and hence higher oral bioavailability.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 475-485 |
| Number of pages | 11 |
| Journal | Pharmaceutical Development and Technology |
| Volume | 19 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2014 |
| Externally published | Yes |
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Keywords
- Caco-2 cells
- Carvedilol
- Cellular uptake mechanism
- Design of experiments
- Oral drug delivery
- Solid lipid nanoparticles
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Preparation, in vitro evaluation and statistical optimization of carvedilol-loaded solid lipid nanoparticles for lymphatic absorption via oral administration. / Shah, Mansi; Madan, Parshotam; Lin, Senshang.
In: Pharmaceutical Development and Technology, Vol. 19, No. 4, 2014, p. 475-485.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Preparation, in vitro evaluation and statistical optimization of carvedilol-loaded solid lipid nanoparticles for lymphatic absorption via oral administration
AU - Shah, Mansi
AU - Madan, Parshotam
AU - Lin, Senshang
PY - 2014
Y1 - 2014
N2 - Carvedilol-loaded solid lipid nanoparticles (SLNs) were prepared using solubility parameter (δ) to select the lipid, and hot homogenization to fabricate SLNs. The effect of concentration of Compritol 888 ATO (COMP) and Poloxamer 188 (P-188) on the particle size of blank SLNs was studied using the design of experiments. Further narrow concentration range of COMP and P- 188 was selected and carvedilol-loaded SLNs were prepared to obtain an optimized formulation which was lyophilized (L-SLNs), transformed into enteric compression-coated tablet and evaluated for drug release, X-ray diffraction and cellular uptake mechanism. COMP was chosen as lipid due to its least value of Δδ with carvedilol. The optimized formulation (7.5% COMP, 5.0% P-188 and 1.11% carvedilol) had 161nm particle size and 94.8% entrapment efficiency. The enteric-coated carvedilol-loaded SLNs tablet protected carvedilol from acidic environment and similar prolonged release profiles were obtained from L-SLNs, core tablet and entericcoated tablet. Absence of crystalline carvedilol XRD peak indicated the presence of amorphous carvedilol in SLNs. Higher carvedilol uptake from SLNs compared to drug solution in the Caco-2 cell line exhibited a potential prolonged drug release. Moreover, upon cellular uptake, SLNs could then enter the lymphatic system which will avoid first pass metabolism and hence higher oral bioavailability.
AB - Carvedilol-loaded solid lipid nanoparticles (SLNs) were prepared using solubility parameter (δ) to select the lipid, and hot homogenization to fabricate SLNs. The effect of concentration of Compritol 888 ATO (COMP) and Poloxamer 188 (P-188) on the particle size of blank SLNs was studied using the design of experiments. Further narrow concentration range of COMP and P- 188 was selected and carvedilol-loaded SLNs were prepared to obtain an optimized formulation which was lyophilized (L-SLNs), transformed into enteric compression-coated tablet and evaluated for drug release, X-ray diffraction and cellular uptake mechanism. COMP was chosen as lipid due to its least value of Δδ with carvedilol. The optimized formulation (7.5% COMP, 5.0% P-188 and 1.11% carvedilol) had 161nm particle size and 94.8% entrapment efficiency. The enteric-coated carvedilol-loaded SLNs tablet protected carvedilol from acidic environment and similar prolonged release profiles were obtained from L-SLNs, core tablet and entericcoated tablet. Absence of crystalline carvedilol XRD peak indicated the presence of amorphous carvedilol in SLNs. Higher carvedilol uptake from SLNs compared to drug solution in the Caco-2 cell line exhibited a potential prolonged drug release. Moreover, upon cellular uptake, SLNs could then enter the lymphatic system which will avoid first pass metabolism and hence higher oral bioavailability.
KW - Caco-2 cells
KW - Carvedilol
KW - Cellular uptake mechanism
KW - Design of experiments
KW - Oral drug delivery
KW - Solid lipid nanoparticles
UR - http://www.scopus.com/inward/record.url?scp=84899909546&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899909546&partnerID=8YFLogxK
U2 - 10.3109/10837450.2013.795169
DO - 10.3109/10837450.2013.795169
M3 - Article
VL - 19
SP - 475
EP - 485
JO - Pharmaceutical Development and Technology
JF - Pharmaceutical Development and Technology
SN - 1083-7450
IS - 4
ER -