A top-down technique to improve the solubility and bioavailability of aceclofenac

In vitro and in vivo studies

Reema Narayan, Abhyuday Pednekar, Dipshikha Bhuyan, Chaitra Gowda, K. B. Koteshwara, Usha Yogendra Nayak

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The aim of the present work was to tackle the solubility issue of a biopharmaceutics classification system (BCS)-II drug, aceclofenac. Although a number of attempts to increase the aqueous solubility have been made, none of the methods were taken up for scale-up. Hence size reduction technique by a top-down approach using wet milling process was utilized to improve the solubility and, consequently, the dissolution velocity of aceclofenac. The quality of the final product was ensured by Quality by Design approach wherein the effects of critical material attributes and critical process parameters were assessed on the critical quality attributes (CQAs) of nanocrystals. Box-Behnken design was applied to evaluate these effects on critical quality attributes. The optimized nanocrystals had a particle size of 484.7±54.12 nm with a polydispersity index (PDI) of 0.108±0.009. The solid state characterization of the formulation revealed that the crystalline nature of the drug was slightly reduced after the milling process. With the reduced particle size, the solubility of the nanocrystals was found to increase in both water and 0.1 N HCl when compared with that of unmilled pure aceclofenac. These results were further supported by in vitro release studies of nanocrystals where an appreciable dissolution velocity with 100.07%±2.38% release was observed for aceclofenac nanocrystals compared with 47.66%±4.53% release for pure unmilled aceclofenac at the end of 2 h. The in vivo pharmacokinetic data generated showed a statistically significant increase in the Cmax for aceclofenac nanocrystals of 3.75±0.28 µg/mL (for pure unmilled aceclofenac Cmax was 1.96±0.17 µg/mL). The results obtained indicated that the developed nanocrystals of aceclofenac were successful in improving the solubility, thus the absorption and bioavailability of the drug. Hence, it may be a viable and cost-effective alternative to the current therapy.

Original languageEnglish
Pages (from-to)4921-4935
Number of pages15
JournalInternational Journal of Nanomedicine
Volume12
DOIs
Publication statusPublished - 11-07-2017

Fingerprint

Solubility
Nanocrystals
Biological Availability
Nanoparticles
Particle Size
Dissolution
Particle size
Strategic materials
Biopharmaceutics
Pharmaceutical Preparations
Pharmacokinetics
Polydispersity
aceclofenac
In Vitro Techniques
Crystalline materials
Costs and Cost Analysis
Water
Costs

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Drug Discovery
  • Organic Chemistry

Cite this

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title = "A top-down technique to improve the solubility and bioavailability of aceclofenac: In vitro and in vivo studies",
abstract = "The aim of the present work was to tackle the solubility issue of a biopharmaceutics classification system (BCS)-II drug, aceclofenac. Although a number of attempts to increase the aqueous solubility have been made, none of the methods were taken up for scale-up. Hence size reduction technique by a top-down approach using wet milling process was utilized to improve the solubility and, consequently, the dissolution velocity of aceclofenac. The quality of the final product was ensured by Quality by Design approach wherein the effects of critical material attributes and critical process parameters were assessed on the critical quality attributes (CQAs) of nanocrystals. Box-Behnken design was applied to evaluate these effects on critical quality attributes. The optimized nanocrystals had a particle size of 484.7±54.12 nm with a polydispersity index (PDI) of 0.108±0.009. The solid state characterization of the formulation revealed that the crystalline nature of the drug was slightly reduced after the milling process. With the reduced particle size, the solubility of the nanocrystals was found to increase in both water and 0.1 N HCl when compared with that of unmilled pure aceclofenac. These results were further supported by in vitro release studies of nanocrystals where an appreciable dissolution velocity with 100.07{\%}±2.38{\%} release was observed for aceclofenac nanocrystals compared with 47.66{\%}±4.53{\%} release for pure unmilled aceclofenac at the end of 2 h. The in vivo pharmacokinetic data generated showed a statistically significant increase in the Cmax for aceclofenac nanocrystals of 3.75±0.28 µg/mL (for pure unmilled aceclofenac Cmax was 1.96±0.17 µg/mL). The results obtained indicated that the developed nanocrystals of aceclofenac were successful in improving the solubility, thus the absorption and bioavailability of the drug. Hence, it may be a viable and cost-effective alternative to the current therapy.",
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A top-down technique to improve the solubility and bioavailability of aceclofenac : In vitro and in vivo studies. / Narayan, Reema; Pednekar, Abhyuday; Bhuyan, Dipshikha; Gowda, Chaitra; Koteshwara, K. B.; Nayak, Usha Yogendra.

In: International Journal of Nanomedicine, Vol. 12, 11.07.2017, p. 4921-4935.

Research output: Contribution to journalArticle

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