Preparation, in vitro evaluation and statistical optimization of carvedilol-loaded solid lipid nanoparticles for lymphatic absorption via oral administration

Mansi Shah, Parshotam Madan, Senshang Lin

Research output: Contribution to journalArticle

27 Scopus citations

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 languageEnglish (US)
Pages (from-to)475-485
Number of pages11
JournalPharmaceutical Development and Technology
Volume19
Issue number4
DOIs
StatePublished - 2014
Externally publishedYes

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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

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