Novel Formulation Strategies for Improving Oral Bioavailability of Drugs with Poor Membrane Permeation or Presystemic Metabolism

Aungst, Bruce J.

doi:10.1002/jps.2600821008

Cited by 186 publications

(94 citation statements)

References 96 publications

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“…Various strategies have been used to overcome the problems associated with oral absorption and bioavailability issues of poorly soluble drugs, such as particle size reduction (Aungst, 1993), complexation with cyclodextrins (Miyake et al, 2000), salt formation, solid dispersions (Sinha et al, 2010), use of surfactant, nanoparticles, nanocarriers (Bali et al, 2011), Nanoemulsions , self-emulsifying drug delivery system , prodrug formation, etc. Approaches used in past to improve the dissolution and bioavailability of NRG include complexation with b-cyclodextrin (Tommasini et al, 2004), phospholipid complexes (Semalty et al, 2010), solid dispersion with PVP (Kanaze et al, 2006), etc.…”

Section: Introductionmentioning

confidence: 99%

Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization,in vitroandin vivoevaluation

et al. 2014

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(2015) Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization, invitro and invivo evaluation, Drug Delivery, 22:4, 552-561, DOI: 10.3109/10717544.2013 Abstract Naringenin (NRG), predominant flavanone in grapefruits, possesses anti-inflammatory, anti-carcinogenic, hepato-protective and anti-lipid peroxidation effects. Slow dissolution after oral ingestion due to its poor solubility in water, as well as low bioavailability following oral administration, restricts its therapeutic application. The study is an attempt to improve the solubility and bioavailability of NRG by employing self-nanoemulsifying drug delivery technique. Preliminary screening was carried out to select oil, surfactant and co-surfactant, based on solubilization and emulsification efficiency of the components. Pseudo ternary phase diagrams were constructed to identify the area of nanoemulsification. The developed selfnanoemulsifying drug delivery systems (SNEDDS) were evaluated in term of goluble size, globule size distribution, zeta potential, and surface morphology of nanoemulsions so obtained. The TEM analysis proves that nanoemulsion shows a droplet size less than 50 nm. Freeze thaw cycling and centrifugation studies were carried out to confirm the stability of the developed SNEDDS. In vitro drug release from SNEDDS was significantly higher (p50.005) than pure drug. Furthermore, area under the drug concentration time-curve (AUC 0-24 ) of NRG from SNEDDS formulation revealed a significant increase (p50.005) in NRG absorption compared to NRG alone. The increase in drug release and bioavailability as compared to drug suspension from SNEDDS formulation may be attributed to the nanosized droplets and enhanced solubility of NRG in the SNEDDS.

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Section: Introductionmentioning

confidence: 99%

Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization,in vitroandin vivoevaluation

et al. 2014

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“…Various formulation strategies are reported in the literature including the use of surfactants, cyclodextrins, nanoparticles, micronisation, lipids and permeation enhancers to enhance the solubility. These strategies are successful in the selected cases and have specific advantages and limitations [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Crystalline and amorphous carvedilol-loaded nanoemulsions: formulation optimisation using response surface methodology

Bhagat

Singh

Verma

et al. 2012

Journal of Experimental Nanoscience

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(2013) Crystalline and amorphous carvedilolloaded nanoemulsions: formulation optimisation using response surface methodology, Journal of Experimental Nanoscience, 8:7-8, 971-992, DOI: 10.1080/17458080.2011 This study aimed to evaluate the crystalline and amorphous carvedilol along with their lipidic mixtures using various instrumental techniques and to use response surface methodology in conjunction with factorial design to establish the functional relationships between operating variables (capmul GMS 50 K and cremophor RH 40). The response variables selected are spectroscopic absorbance (Y 1 ), mean particle size in distilled water (Y 2 ) and in phosphate buffer pH 6.8 (Y 3 ), polydispersibility index (PDI) (Y 4 ) and zeta potential (Y 5 ). The optimal formulations of crystalline and amorphous carvedilol-loaded nanoemulsions were composed of fixed levels, À0.41 and À0.42, of capmul GMS 50 K and cremophor RH 40, respectively. The predicted and observed values of Y 1 -Y 5 for blank nanoemulsions showed the percentage bias error of À12.12%, À10.25%, À18.47%, þ14.81 and À2.89, respectively. The bias percent ranged between À2.70% and À29.41% for the responses Y 1 -Y 4 for both crystalline and amorphous carvedilol-loaded nanoemulsions, indicating high degree of prognosis. However, the bias percent values for the response variable Y 5 were 294.2% and 262.6%, for the crystalline and amorphous carvedilol-loaded nanoemulsions, respectively, possibly due to cationisation of emulsion droplets. The transmission electron microscopy of selected optimal nanoemulsions showed the spherical shape of globules with no signs of coalescence and precipitation of drug. This study demonstrates the use of factorial design for the preparation of nanoemulsions of crystalline and amorphous carvedilol. The desirable goals can be obtained by systematic formulation approach in the shortest possible time.

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“…Liposomes are enclosed vesicles composed of phosphatidylcholine and cholesterol lipid bilayers, which have been extensively studied as drug carriers [7,8] . The similarity between liposomal lipid bilayers and biomembranes and the relatively small size of liposomes significantly facilitate their oral absorption [9] . However, liposomes still lack a significant medical impact despite a relatively long history of investigation.…”

Section: Introductionmentioning

confidence: 99%

Proliposomes for oral delivery of dehydrosilymarin: preparation and evaluation in vitro and in vivo

Chu

Tong

et al. 2011

Acta Pharmacol Sin

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Aim: To formulate proliposomes with a polyphase dispersed system composed of soybean phospholipids, cholesterol, isopropyl myristate and sodium cholate to improve the oral bioavailability of dehydrosilymarin, an oxidized form of herbal drug silymarin. Methods: Dehydrosilymarin was synthesized from air oxidation of silymarin in the presence of pyridine, and proliposomes were prepared by a film dispersion-freeze drying method. Morphological characterization of proliposomes was observed using a transmission electron microscope. Particle size and encapsulation efficiency of proliposomes were measured. The in vitro release of dehydrosilymarin from suspension and proliposomes was evaluated. The oral bioavailability of dehydrosilymarin suspension and proliposomes was investigated in rabbits. Results: The proliposomes prepared under the optimum conditions were spherical and smooth with a mean particle size in the range of 7 to 50 nm. Encapsulation efficiency was 81.59%±0.24%. The in vitro accumulative release percent of dehydrosilymarinloaded proliposomes was stable, which was slow in pH 1.2, and increased continuously in pH 6.8, and finally reached 86.41% at 12 h. After oral administration in rabbits, the relative bioavailability of proliposomes versus suspension in rabbits was 228.85%. Conclusion: Proliposomes may be a useful vehicle for oral delivery of dehydrosilymarin, a drug poorly soluble in water.

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Novel Formulation Strategies for Improving Oral Bioavailability of Drugs with Poor Membrane Permeation or Presystemic Metabolism

Cited by 186 publications

References 96 publications

Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization,in vitroandin vivoevaluation

Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization,in vitroandin vivoevaluation

Crystalline and amorphous carvedilol-loaded nanoemulsions: formulation optimisation using response surface methodology

Proliposomes for oral delivery of dehydrosilymarin: preparation and evaluation in vitro and in vivo

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