Development and in vivo evaluation of child-friendly lopinavir/ritonavir pediatric granules utilizing novel in situ self-assembly nanoparticles

Kevin Pham, Diana Li, Shujie Guo, Scott Robert Penzak, Xiaowei Dong

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The aim of this study was to develop a nanotechnology to formulate a fixed-dose combination of poorly water-soluble drugs in a children-friendly, flexible solid dosage form. For diseases like HIV, pediatric patients are taking multiple drugs for effective treatments. Fixed-dose combinations could reduce pill burdens and costs as well as improving patient adherence. However, development of fixed-dose combinations of poorly water-soluble drugs for pediatric formulations is very challenging. We discovered a novel nanotechnology that produced in situ self-assembly nanoparticles (ISNPs) when the ISNP granules were introduced to water. In this study, antiretroviral drug granules, including lopinavir (LPV) ISNP granules and a fixed-dose combination of LPV/ritonavir (RTV) ISNP granules, were prepared using the ISNP nanotechnology, which spontaneously produced drug-loaded ISNPs in contact with water. Drug-loaded ISNPs had particle size less than 158 nm with mono-dispersed distribution, over 95% entrapment efficiency for both LPV and RTV and stability over 8 h in simulated physiological conditions. Drug-loaded ISNP granules with about 16% of LPV and 4% of RTV were palatable and stable at room temperature over 6 months. Furthermore, LPV/RTV ISNP granules displayed a 2.56-fold increase in bioavailability and significantly increased LPV concentrations in tested tissues, especially in HIV sanctuary sites, as compared to the commercial LPV/RTV tablet (Kaletra®) in rats. Overall, the results demonstrated that the novel ISNP nanotechnology is a promising platform to manufacture palatable, "heat" stable, and flexible pediatric granules for fixed-dose combinations that can be used as sachets and sprinkles. To the best of our knowledge, this is the first report on this kind of novel nanotechnology for pediatric fixed-dose combinations of poorly water-soluble drugs.

Original languageEnglish
Pages (from-to)88-97
Number of pages10
JournalJournal of Controlled Release
Volume226
DOIs
StatePublished - 28 Mar 2016

Fingerprint

Lopinavir
Ritonavir
Nanoparticles
Pediatrics
Nanotechnology
Pharmaceutical Preparations
Water
HIV
Drug Compounding
Dosage Forms
Patient Compliance
Particle Size
Biological Availability
Tablets
Hot Temperature

Keywords

  • Drug loading
  • Fixed-dose combinations
  • HIV
  • Pediatric formulation
  • Stability
  • Taste

Cite this

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title = "Development and in vivo evaluation of child-friendly lopinavir/ritonavir pediatric granules utilizing novel in situ self-assembly nanoparticles",
abstract = "The aim of this study was to develop a nanotechnology to formulate a fixed-dose combination of poorly water-soluble drugs in a children-friendly, flexible solid dosage form. For diseases like HIV, pediatric patients are taking multiple drugs for effective treatments. Fixed-dose combinations could reduce pill burdens and costs as well as improving patient adherence. However, development of fixed-dose combinations of poorly water-soluble drugs for pediatric formulations is very challenging. We discovered a novel nanotechnology that produced in situ self-assembly nanoparticles (ISNPs) when the ISNP granules were introduced to water. In this study, antiretroviral drug granules, including lopinavir (LPV) ISNP granules and a fixed-dose combination of LPV/ritonavir (RTV) ISNP granules, were prepared using the ISNP nanotechnology, which spontaneously produced drug-loaded ISNPs in contact with water. Drug-loaded ISNPs had particle size less than 158 nm with mono-dispersed distribution, over 95{\%} entrapment efficiency for both LPV and RTV and stability over 8 h in simulated physiological conditions. Drug-loaded ISNP granules with about 16{\%} of LPV and 4{\%} of RTV were palatable and stable at room temperature over 6 months. Furthermore, LPV/RTV ISNP granules displayed a 2.56-fold increase in bioavailability and significantly increased LPV concentrations in tested tissues, especially in HIV sanctuary sites, as compared to the commercial LPV/RTV tablet (Kaletra{\circledR}) in rats. Overall, the results demonstrated that the novel ISNP nanotechnology is a promising platform to manufacture palatable, {"}heat{"} stable, and flexible pediatric granules for fixed-dose combinations that can be used as sachets and sprinkles. To the best of our knowledge, this is the first report on this kind of novel nanotechnology for pediatric fixed-dose combinations of poorly water-soluble drugs.",
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Development and in vivo evaluation of child-friendly lopinavir/ritonavir pediatric granules utilizing novel in situ self-assembly nanoparticles. / Pham, Kevin; Li, Diana; Guo, Shujie; Penzak, Scott Robert; Dong, Xiaowei.

In: Journal of Controlled Release, Vol. 226, 28.03.2016, p. 88-97.

Research output: Contribution to journalArticle

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