Solid self-nanoemulsifying drug delivery system (S-SNEDDS) of darunavir for improved dissolution and oral bioavailability: In vitro and in vivo evaluation

Inugala, Spandana; Eedara, Basanth Babu; Sunkavalli, Sharath; Dhurke, Rajeshri; Kandadi, Prabhakar; Jukanti, Raju; Bandari, Suresh

doi:10.1016/j.ejps.2015.03.024

Cited by 154 publications

(87 citation statements)

References 41 publications

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“…In summary, low- (0.4%), medium- (2%), and high-dose (10%) simvastatin with or without 2% cholesterol were prepared in Transcutol/Capmul MCM EP 1:1 (v:v) 21,30–32 for topical application. Fourteen rabbits were used for simvastatin topical treatment, with 2, 6, 3, and 3 rabbits for 0.4%, 2%, 10% simvastatin, and 10% simvastatin with 2% cholesterol treatments, respectively, totaling 84 treated and 84 control wounds (6 wounds per ear).…”

Section: Methodsmentioning

confidence: 99%

Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model

Song

Xie

Hong

et al. 2017

Plastic and Reconstructive Surgery - Global Open

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Background:We previously showed that intradermal injection of statins is a successful treatment for hypertrophic scarring. Topical application has many advantages over intradermal injection. In this study, we demonstrate the efficacy of topical statin treatment in reducing scar in our validated rabbit ear scar model.Methods:Twenty New Zealand White rabbits were divided into 2 study groups, with 6 rabbits receiving 10 μm pravastatin intradermally at postoperative days 15, 18, and 21, and 14 rabbits receiving 0.4%, 2%, and 10% simvastatin topical application at postoperative days 14–25. Four or 6 full-thickness circular dermal punches 7 mm in diameter were made on the ventral surface of the ear down to but not including the perichondrium. Specimens were collected at 28 days to evaluate the effects of statins on hypertrophic scarring.Results:Treatment with pravastatin intradermal administration significantly reduced scarring in terms of scar elevation index. Topical treatment with both medium- and high-dose simvastatin also significantly reduced scarring. High-dose simvastatin topical treatment showed a major effect in scar reduction but induced side effects of scaling, erythema, and epidermal hyperplasia, which were improved with coapplication of cholesterol. There is a dose response in scar reduction with low-, medium- and high-dose simvastatin topical treatment. High-dose simvastatin treatment significantly reduced the messenger ribonucleic acid (mRNA) expression of connective tissue growth factor, consistent with our previously published work on intradermally injected statins. More directly, high-dose simvastatin treatment also significantly reduced the mRNA expression of collagen 1A1.Conclusions:Topical simvastatin significantly reduces scar formation. The mechanism of efficacy for statin treatment through interference with connective tissue growth factor mRNA expression was confirmed.

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Section: Methodsmentioning

confidence: 99%

Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model

Song

Xie

Hong

et al. 2017

Plastic and Reconstructive Surgery - Global Open

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“…Darunavir, a poorly soluble drug was formulated as liquid SNEDDS (L-SNEDDS) containing Capmul MCM (a medium chain triglyceride) followed by conversion to a solid powder (S-SNEDDS) (Inugala et al, 2015). The in vivo studies showed $2-2.5 times higher C max and 2-3 times higher AUC 0-values obtained after oral administration of L-SNEDDS and S-SNEDDS to Wistar albino rats compared to normal drug suspension.…”

Section: Effect Of Final Dosage Forms (Liquid and Solid) Of Sedds/smementioning

confidence: 99%

Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view

et al. 2016

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Self-emulsifying drug delivery system (SEDDS) is an isotropic mixture of lipid, surfactant and co-surfactant, which forms a fine emulsion when comes in contact of an aqueous medium with mild agitation. SEDDS is considered as a potential platform for oral delivery of hydrophobic drug in order to overcome their poor and irregular bioavailability challenges. In spite of fewer advantages like improved solubility of drug, bypassing lymphatic transport etc., SEDDS faces different controversial issues such as the use of appropriate terminology (self-microemulsifying drug delivery system; SMEDDS or self-nanoemulsifying drug delivery system; SNEDDS), presence of high amount of surfactant, correlation of in vitro model to in vivo studies, lack of human volunteer study and effect of conversion of SEDDS to final administrable dosage form on pharmacokinetic behavior of the drug. In this review, potential issues or questions on SEDDS are identified and summarized from the pharmacokinetic point of view. Primarily this review includes the conflict between the influences of droplet size, variation in correlation between in vitro lipolysis or ex-vivo intestinal permeation and pharmacokinetic parameters, variation in in vivo results of solid and liquid SEDDS, and potential challenges or limitation of pharmacokinetic studies on human volunteers with orally administered SEDDS. In the past decades, hundreds of in vivo studies on SEDDS have been published. In the present study, only the relevant article on in vivo pharmacokinetic studies with orally administered SEDDS published in past 5-6 years are analyzed for an up to date compilation. KeywordsPoor bioavailability, self-nanoemulsifying delivery system, self-microemulsifying delivery system, in vitro lipolysis, pharmacokinetic of SEDDS History

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“…Upon incorporation of cuminaldehyde into SEN (Figure c), the characteristic absorption peaks of cuminaldehyde at 1701.85, 1607.71 and 833.65 cm −1 were retained with broad bands of the excipients while other peaks of the pure drug disappeared. The disappearance of characteristic peaks of cuminaldehyde might be ascribed to the overlapping of drug peaks with that of the excipients …”

Section: Resultsmentioning

confidence: 99%

“…The PDI and ZP of CuA‐SEN also varied minimally after storage at the same climatic conditions (Table ). Generally, CuA‐SEN is classified as thermodynamically stable with no signs of phase‐separation, haziness or precipitation . Thus, the stability of cuminaldehyde can be enhanced with SEN nanocarrier.…”

Section: Resultsmentioning

confidence: 99%

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Novel cuminaldehyde self-emulsified nanoemulsion for enhanced antihepatotoxicity in carbon tetrachloride-treated mice

Adu‐Frimpong

Wei

Firempong

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives Cuminaldehyde self‐emulsified nanoemulsion (CuA‐SEN) was prepared and optimised to improve its oral bioavailability and antihepatotoxicity. Methods Cuminaldehyde self‐emulsified nanoemulsion was developed through the self‐nanoemulsification method using Box–Behnken Design (BBD) tool while appropriate physicochemical indices were evaluated. The optimised CuA‐SEN was characterised via droplet size (DS), morphology, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, in‐vitro release, and pharmacokinetic studies while its antihepatotoxicity was evaluated. Key findings Cuminaldehyde self‐emulsified nanoemulsion with acceptable characteristics (mean DS‐48.83 ± 1.06 nm; PDI‐0.232 ± 0.140; ZP‐29.92 ± 1.66 mV; EE‐91.51 ± 0.44%; and drug‐loading capacity (DL)‐9.77 ± 0.75%) was formulated. In‐vitro drug release of CuA‐SEN significantly increased with an oral relative bioavailability of 171.02%. Oral administration of CuA‐SEN to CCl4‐induced hepatotoxicity mice markedly increased the levels of superoxide dismutase, glutathione and catalase in serum. Also, CuA‐SEN reduced the levels of tumour necrosis factor‐alpha and interleukin‐6 in both serum and liver tissues while aspartate aminotransferase, alanine aminotransferase and malonaldehyde levels were significantly decreased. Conclusions These findings showed that the improved bioavailability of cuminaldehyde via SEN provided an effective approach for enhancing antioxidation, anti‐inflammation and antihepatotoxicity of the drug.

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Solid self-nanoemulsifying drug delivery system (S-SNEDDS) of darunavir for improved dissolution and oral bioavailability: In vitro and in vivo evaluation

Cited by 154 publications

References 41 publications

Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model

Local Application of Statins Significantly Reduced Hypertrophic Scarring in a Rabbit Ear Model

Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view

Novel cuminaldehyde self-emulsified nanoemulsion for enhanced antihepatotoxicity in carbon tetrachloride-treated mice

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