title: Mesoporous silica-based dosage forms improve release characteristics of poorly soluble drugs: case example fenofibrate.
abstract: OBJECTIVE
  Mesoporous silica-based dosage forms offer the potential for improving the absorption of poorly soluble drugs after oral administration. In this investigation, fenofibrate was used as a model drug to study the ability of monomodal ('PSP A') and bimodal ('PSP B') porous silica to improve release by a 'spring' effect in in vitro biorelevant dissolution tests. Also investigated was the addition of various polymers to provide a 'parachute' effect, that is, to keep the drug in solution after its release.
  
  
  RESULTS
  Loading fenofibrate onto PSP A or PSP B porous silica substantially improved the dissolution profile of fenofibrate under fasted state conditions compared with both pure drug and the marketed product, TriCor® 145 mg. Adding a polymer such as hydroxypropyl methylcellulose acetate succinate, polyvinylpyrrolidone or copovidon (HPMCAS, PVP or PVPVA) sustains the higher release of fenofibrate from the PSP A silica, resulting in a combination 'spring and parachute' effect - loading the drug onto the silica causes a 'spring' effect while the polymer enhances the spring effect (HPMCAS, PVP) and adds a sustaining 'parachute'. Interestingly, a silica to polymer ratio of 4:1 w/w appears to have an optimal effect for fenofibrate (HPMCAS, PVP). Dissolution results under conditions simulating the fasted state in the small intestine with the PSP A or the PSP B silica with HPMCAS added in a 4:1 w/w ratio show very substantial improvement over the marketed, nanosized product (TriCor® 145 mg).
  
  
  CONCLUSIONS
  Further experiments to determine whether the highly positive effects on fenofibrate release observed with the silica prototypes investigated to date can be translated to further poorly soluble drugs and to what extent they translate into improved in-vivo performance are warranted.
authors.affiliation: Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Dressman
authors.affiliation: Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Herbert
authors.affiliation: Formulation Research and Development, Merck Millipore, Merck KGaA, Darmstadt, Germany.
authors.forename: Alena
authors.initials: A
authors.lastname: Wieber
authors.affiliation: Formulation Research and Development, Merck Millipore, Merck KGaA, Darmstadt, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Birk
authors.affiliation: Bioanalytical Chemistry, Merck KGaA, Darmstadt, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Saal
authors.affiliation: Formulation Research and Development, Merck Millipore, Merck KGaA, Darmstadt, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Lubda
mesh_terms: D003692:Delayed-Action Preparations; D004339:Drug Compounding; D005215:Fasting; D011345:Fenofibrate / Q000737:chemistry*; D005750:Gastric Juice / Q000737:chemistry; D000960:Hypolipidemic Agents / Q000737:chemistry*; D065347:Hypromellose Derivatives / Q000737:chemistry; D007419:Intestinal Secretions / Q000737:chemistry; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008956:Models, Chemical; D053758:Nanoparticles; D010316:Particle Size; D016062:Porosity; D011205:Povidone / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014753:Vinyl Compounds / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D000960:Hypolipidemic Agents; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D065347:Hypromellose Derivatives; C048331:hydroxypropylmethylcellulose acetate succinate; D012822:Silicon Dioxide; D008747:Methylcellulose; D011205:Povidone; D011345:Fenofibrate
keywords: biorelevant media; dissolution; fenofibrate; mesoporous silica; poorly soluble drugs