Remember Me
Or use your Academic/Social account:


Or use your Academic/Social account:


You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.


Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message


Verify Password:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Muees, Joke; Scurr, David J.; Amssoms, Katie; Annaert, Pieter; Davies, Martyn C.; Roberts, Clive J.; Mooter, Guy Van den (2015)
Publisher: Elsevier
Languages: English
Types: Article

Classified by OpenAIRE into

mesheuropmc: technology, industry, and agriculture, macromolecular substances
At present no scientific rationale exists for selecting a particular enabling strategy to formulate a poorly water-soluble drug, although this is crucial as it will influence the in vivo performance of the resulting formulation. This study provides an insight into this complicated decision making process for a poorly soluble human immunodeficiency virus (HIV) protease inhibitor based upon in vivo test results. A formulation strategy based on the molecular dispersion of this active pharmaceutical ingredient (API) into a biphasic matrix consisting of water-insoluble poly(lactic-co-glycolic acid) (PLGA) and water-soluble polyvinylpyrrolidone (PVP) was evaluated. The long-term in vivo performance of this strategy was compared to that of other solubility enhancing approaches by evaluating the exposure in male Beagle dogs. Solid dispersions, based on a PLGA/PVP matrix, were compared to solid dispersions in a pure water-insoluble PLGA matrix. Additionally these solid dispersion strategies were compared to the strategy of particle size reduction by means of an API microsuspension. The in vivo performance of the various formulations over a period of 28 days after intramuscular injection was evaluated by the observed initial burst release, plasma concentration-time profiles, time at which maximum plasma levels were reached (tmax,obs) and the estimated bioavailability. Compared to the other formulation strategies assessed, it was concluded that the addition of PVP in a PLGA matrix resulted in vivo in a more sustained release as well as a higher amount of drug released from the polymeric matrix. This was explained based on the structure of these binary PLGA/PVP matrices where the pore network originating from rapidly dissolving PVP plays a crucial role. Moreover, the results suggest that the release of this type of formulations could be delayed by increasing the amount of PLGA in the formulation.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • [1] [2] [3] [4] [5] [6] [7] [8] [9] H.D. Williams, N.L. Trevaskis, S. a Charman, R.M. Shanker, W.N. Charman, C.W.
    • Pouton, et al., Strategies to address low drug solubility in discovery and development., Pharmacol. Rev. 65 (2013) 315-499.
    • G. van 't Klooster, E. Hoeben, H. Borghys, A. Looszova, M.-P. Bouche, F. van Velsen, et al., Pharmacokinetics and disposition of rilpivirine (TMC278) nanosuspension as a long-acting injectable antiretroviral formulation., Antimicrob. Agents Chemother. 54 (2010) 2042-50. doi:10.1128/AAC.01529-09.
    • J. Meeus, X. Chen, D.J. Scurr, V. Ciarnelli, K. Amssoms, C.J. Roberts, et al., Nanoscale surface characterization and miscibility study of a spray-dried injectable polymeric matrix consisting of poly(lactic-co-glycolic acid) and polyvinylpyrrolidone., J. Pharm. Sci. 101 (2012) 3473-85. doi:10.1002/jps.23131.
    • J. Meeus, D.J. Scurr, K. Amssoms, M.C. Davies, C.J. Roberts, G. Van den Mooter, Surface characteristics of spray-dried microspheres consisting of PLGA and PVP: relating the influence of heat and humidity to the thermal characteristics of these polymers., Mol. Pharm. 10 (2013) 3213-24. doi:10.1021/mp400263d.
    • B. Twaites, C. de las Heras Alarc n, C. Alexander, Synthetic polymers as drugs and therapeutics, J. Mater. Chem. 15 (2005) 441. doi:10.1039/b410799n.
    • M. Eerdekens, I. Van Hove, B. Remmerie, E. Mannaert, Pharmacokinetics and tolerability of long-acting risperidone in schizophrenia., Schizophr. Res. 70 (2004) 91- 100. doi:10.1016/j.schres.2003.11.001.
    • B.E. Rabinow, Nanosuspensions in drug delivery., Nat. Rev. Drug Discov. 3 (2004) 785-96. doi:10.1038/nrd1494.
    • E. Merisko-Liversidge, G.G. Liversidge, E.R. Cooper, Nanosizing: a formulation approach for poorly-water-soluble compounds., Eur. J. Pharm. Sci. 18 (2003) 113-20.
    • L. Citrome, Paliperidone palmitate - review of the efficacy, safety and cost of a new second-generation depot antipsychotic medication., Int. J. Clin. Pract. 64 (2010) 216- 39. doi:10.1111/j.1742-1241.2009.02240.x.
    • [10] K. Tziomalos, V.G. Athyros, Fenofibrate: a novel formulation (Triglide) in the treatment of lipid disorders: a review., Int. J. Nanomedicine. 1 (2006) 129-47.
    • [11] J. Meeus, D.J. Scurr, K. Amssoms, P. Annaert, M.C. Davies, C.J. Roberts, et al., Physicochemical characterization and in vitro evaluation of various formulation strategies for sustained release injectables of poorly soluble HIV protease inhibitor, (n.d.).
    • L. Baert, G. van 't Klooster, W. Dries, M. Fran├žois, A. Wouters, E. Basstanie, et al., Development of a long-acting injectable formulation with nanoparticles of rilpivirine (TMC278) for HIV treatment., Eur. J. Pharm. Biopharm. 72 (2009) 502-8.
    • doi:10.1016/j.ejpb.2009.03.006.
  • No related research data.
  • No similar publications.

Share - Bookmark

Cite this article