Investigation of the Particle Growth of Fenofibrate following Antisolvent Precipitation and Freeze–Drying (original) (raw)
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Crystal Growth & Design, 2015
Submicron to small-micron sized particles of the hydrophobic drug, fenofibrate, were prepared by controlled crystallisation in order to influence its dissolution behaviour. An antisolvent precipitation process successfully generated particles (200-300 nm) which matched the size and dissolution behaviour of a commercial wet-milled formulation of the drug. Although the preparation of submicron sized particles was straightforward, retaining their size in suspension and during isolation was a challenge. Additives were employed to temporarily stabilise the suspension, and extend the time window for isolation of the submicron particles. Precipitated particles were isolated primarily by immediate freeze-drying, but drying stresses were found to destabilise the fragile submicron system. The growth pathway of particles in suspension, and during oven and freeze-drying were compared. Although the growth pathways appeared considerably different from a visual morphological perspective, an investigation of the
ENHANCING SOLUBILITY AND DISSOLUTION OF FENOFIBRATE BY SPRAY DRYING TECHNIQUE Original Article
International Journal of Pharmacy and Pharmaceutical Sciences, 2015
Objective: Fenofibrate, a hypolipidemic drug agent, exhibits poor water solubility and dissolution. Thus, the aim of the present study was to improve the solubility and dissolution rate of Fenofibrate by preparing microspheres by spray drying technique using Pluronic F-127. Methods: Fenofibrate Microspheres containing different ratios of Pluronic F-127 were produced by spray drying using Chloroform as solvent to enhance solubility and dissolution rate. The prepared formulations containing different ratios of drug and Pluronic F-127were evaluated for solubility and in-vitro dissolution. The prepared formulations were characterized by DSC, FT-IR, XRD and SEM. Dissolution profile of the prepared spray dried microspheres was compared with its physical mixture and the pure sample. Results: Spray dried microspheres exhibited decreased crystallinity. The solubility of microspheres containing Fenofibrate and Pluronic F-127(1:3w/w) exhibited three tenfold increases than the commercial Fenofibrate and dissolution of the same ratio microsphere showed 99 % release in 40 min. While same composition in physical mixture showed 37% release in 20 min. Conclusion: Consequently, from the above result it can be concluded that spray dried microspheres of Fenofibrate is a useful technique to improve the solubility and dissolution of poor water soluble drug like Fenofibrate.
Enhancing Solubility and Dissolution of Fenofibrate by Spray Drying Technique
International Journal of Pharmacy and Pharmaceutical Sciences, 2014
Objective: Fenofibrate, a hypolipidemic drug agent, exhibits poor water solubility and dissolution. Thus, the aim of the present study was to improve the solubility and dissolution rate of Fenofibrate by preparing microspheres by spray drying technique using Pluronic F-127. Methods: Fenofibrate Microspheres containing different ratios of Pluronic F-127 were produced by spray drying using Chloroform as solvent to enhance solubility and dissolution rate. The prepared formulations containing different ratios of drug and Pluronic F-127were evaluated for solubility and in-vitro dissolution. The prepared formulations were characterized by DSC, FT-IR, XRD and SEM. Dissolution profile of the prepared spray dried microspheres was compared with its physical mixture and the pure sample. Results: Spray dried microspheres exhibited decreased crystallinity. The solubility of microspheres containing Fenofibrate and Pluronic F-127(1:3w/w) exhibited three tenfold increases than the commercial Fenofibrate and dissolution of the same ratio microsphere showed 99 % release in 40 min. While same composition in physical mixture showed 37% release in 20 min. Conclusion: Consequently, from the above result it can be concluded that spray dried microspheres of Fenofibrate is a useful technique to improve the solubility and dissolution of poor water soluble drug like Fenofibrate.
Effect of powder processing on performance of fenofibrate formulations
European Journal of Pharmaceutics and Biopharmaceutics, 2008
In this study, the effect of the order in which powder blending and jet-milling were performed for the production of the bulk powders on the performance of 200-mg dose orally disintegrating tablets (ODTs) of fenofibrate was evaluated. Bulk powders composed of fenofibrate, mannitol, copovidone S630, and docusate sodium in a 10:10:2:1.2 ratio were prepared by the following three processes: process A: fenofibrate + excipients fi blending; process B: fenofibrate fi jet-milling fi blending with excipients; process C: fenofibrate + excipients fi blending fi jet-milling. The bulk powders were granulated followed by blending and tableting. The materials were tested for Differential Scanning Calorimetry (DSC), drug particle sizing post-reconstitution, dissolution, optical micrography, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS) and disintegration of the ODTs. It was found that the crystallinity of fenofibrate was not impacted by the blending and jet-milling processes. Process A produced materials having poorer fenofibrate reconstitution as compared to processes involving jet-milling. It was discovered that milling a blend of fenofibrate/excipient (process C) was advantageous over milling the raw drug alone (process B). Process C yielded bulk powder that showed rapid dissolution and ODTs which exhibited rapid disintegration.
Preparation of Fenofibrate Microparticles Using Top-down and Bottom-up Processes
Procedia Chemistry 9:257–264, 2014
Micronization of fenofibrate using top-down process via jet mill and bottom-up process via rapid expansion of supercritical solution (RESS) was conducted to investigate their effects on the formation of micronized fenofibrate. Processed fenofibrate retained its crystalline structure and have similar chemical structure with unprocessed fenofibrate. The average particle size of fenofibrate was reduced from its original wherein from 68.779±0.146 μm to 3.050±0.085 μm using jet mill process at SFR 2.7 kg/h; and to 3.044±0.056 μm using RESS under the optimum condition. The results revealed that jet mill and RESS processes were applicable for micronization of fenofibrate.
Particle engineering of fenofibrate for advanced drug delivery system
Future Journal of Pharmaceutical Sciences, 2019
Background: The goal of the current investigation was to formulate, evaluate co-crystal, and further design of solid unit dosage form of antihyperlipidemic BCS class II drug fenofibrate (FNO). Co-crystals composed of a structurally homogeneous crystalline material that contains two or more components in a definite stoichiometric amount helps in increasing yield, the capability to regulator polymorph fabrication, enhanced invention crystallinity. Ball milling method is used for co-crystal formulation, optimized via 3 2 full factorial design and characterized by saturation solubility, particle size analysis, Fourier transform infrared spectroscopy (FT-IR) study analysis, powder X-ray diffraction (PXRD) study analysis, surface morphology by scanning electron microscopy (SEM) study, flow properties, and ex vivo intestinal permeation study via non-everted rat intestinal sac model. Furthermore, optimized batch compressed into tablets is evaluated for disintegration time, hardness, friability, in vitro drug release study and stability study. Results: It demonstrated that co-crystal formulation FNOCC7 shows higher saturation solubility 0.3874 ± 2.82 g/ml with less particle size 221.231 ± 0.456 nm, FT-IR spectra confirmed significant structural alterations in the formulation indicating the hetero-molecular interaction, the presence of hydrogen bonding had occurred in the cocrystals, PXRD spectra of formulation determined by the increase in the crystalline nature. FNO co-crystals show flux (F) and permeability coefficient (P app) 0.322 ± 0.068 μg/min, 5.38 ± 0.093 cm/min respectively increased compared to the pure drug makes in an enhancement of solubility as well as the bioavailability of BCS class II drug. Conclusions: The solubility and dissolution percentage of FNO can be improved by the utilization of Co-crystal of FNO with PEG 4000. The solubilization impact of PEG 4000 might be contributed because of the decrease of molecule conglomeration of the drug presence of crystallinity, expanded wettability, and dispersibility; pharmaceutical co-crystals speak to a beneficial class of crystal form with regard of pharmaceuticals.
Dissolution rate enhancement of fenofibrate using liquisolid tablet technique
Lat. Am. J. …, 2009
Fenofibrate is more effective drug as compared to other fibrates. But low bioavailability of it is due to its poor aqueous solubility. The purpose of present study was to improve fenofibrate dissolution through its formulation into liquisolid tablets and then to investigate in vitro performance of prepared liquisolid systems. By use of this technique, liquid medications such as solutions or suspensions of water insoluble drugs in suitable non-volatile liquid vehicles can be easily converted into powders with acceptable flow properties and compression behavior by using suitable powder excipients. X-ray powder diffraction and Differential Scanning Calorimetry were used for evaluation of physicochemical properties of Fenofibrate in liquisolid tablets. Stereomicroscopy was used to assess morphological characteristics of liquisolid formulation. Enhanced drug release profiles due to increased wetting properties and surface of drug available for dissolution was obtained in case of liquisolid tablets.
Formulation Development and In Vitro Evaluation of Immediate Release Fenofibrate Pellets
2014
The present study was aimed to formulate and evaluate immediate release fenofibrate pellets using pan coater. Fenofibrate, anti lipidemic drug, being water insoluble with a half life of 22.1 h suitable to develop immediate release pellets for the treatment of primary hypercholesterolemia. Eight formulations (F1-F8) of fenofibrate pellets were prepared using a combination of PVPK 30 as binder and starch as a disintegrant. The prepared pellets were subjected to micrometric properties and In vitro drug release studies. The optimized formulation, F8, showed 99.1% drug release in 30 min. Scanning electron microscopy (SEM) studies showed that the prepared pellets are spherical in shape. The release profile for optimized formulation (F8) was comparable and found higher release than the marketed formulation (LIPICARD) for fenofibrate. The mathematical model was built on the hypotheses that drug diffusion and drug dissolution in the release environment are the key phenomena affecting drug re...