Praziquantel (PZQ), an anthelminthic drug widely used in developing countries, is classified in Class II in the Biopharmaceutics Classification Systems; this means that PZQ has very low water solubility and high permeability, thus the dissolution is the absorption rate-limiting factor. The aim of this work was to evaluate the suitability of melt granulation and ultrasonic spray congealing as techniques for enhancing the dissolution rate of PZQ. Granules in high shear mixer were prepared by melt granulation, using polyethylene glycol 4000 or poloxamer 188 as meltable binders and lactose monohydrate as a filler. Quite regularly shaped granules having main size fraction in the range 200–500 m were obtained using both formulations; however, only poloxamer 188 granules demonstrated a significant (P = 0.05) increase of the PZQ dissolution rate compared to pure drug. To evaluate the potential of ultrasonic spray congealing, Gelucire 50/13 microparticles having different drug to carrier ratios (5, 10, 20 and 30%, w/w) were then prepared. The results showed that all the microparticles had a significant higher dissolution rate (P = 0.05) respect to pure PZQ. The microparticle’s characterisation, performed by DSC, HSM, XRD and FTIR evidenced the absence of both modifications of the solid state of PZQ and of significant interactions between the drug and the carrier. In conclusion, melt granulation and ultrasonic spray congealing could be proposed as solvent free, rapid and low expensive manufacturing methods to increase the in vitro dissolution rate of PZQ. © 2006 Elsevier B.V. All rights reserved.
Evaluation of melt granulation and ultrasonic spray congealing as techniques to enhance the dissolution of praziquantel.
PERISSUTTI, Beatrice;
2006-01-01
Abstract
Praziquantel (PZQ), an anthelminthic drug widely used in developing countries, is classified in Class II in the Biopharmaceutics Classification Systems; this means that PZQ has very low water solubility and high permeability, thus the dissolution is the absorption rate-limiting factor. The aim of this work was to evaluate the suitability of melt granulation and ultrasonic spray congealing as techniques for enhancing the dissolution rate of PZQ. Granules in high shear mixer were prepared by melt granulation, using polyethylene glycol 4000 or poloxamer 188 as meltable binders and lactose monohydrate as a filler. Quite regularly shaped granules having main size fraction in the range 200–500 m were obtained using both formulations; however, only poloxamer 188 granules demonstrated a significant (P = 0.05) increase of the PZQ dissolution rate compared to pure drug. To evaluate the potential of ultrasonic spray congealing, Gelucire 50/13 microparticles having different drug to carrier ratios (5, 10, 20 and 30%, w/w) were then prepared. The results showed that all the microparticles had a significant higher dissolution rate (P = 0.05) respect to pure PZQ. The microparticle’s characterisation, performed by DSC, HSM, XRD and FTIR evidenced the absence of both modifications of the solid state of PZQ and of significant interactions between the drug and the carrier. In conclusion, melt granulation and ultrasonic spray congealing could be proposed as solvent free, rapid and low expensive manufacturing methods to increase the in vitro dissolution rate of PZQ. © 2006 Elsevier B.V. All rights reserved.Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
