Development of solidified self-microemulsifying delivery systems with enhanced stability of sirolimus and extended release

Tao, Chun; Chen, Juming; Huang, Aiwen; Zhang, Jing; Lin, Bangjiang; Liu, Zhihong; Zhang, Minxin; Chen, Xu; Zeng, Liang; Zhang, Ling-Na; Hong-tao, Song

doi:10.1016/j.ijpharm.2016.09.035

Cited by 15 publications

(9 citation statements)

References 15 publications

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“…Several workers have used combinations of MCC with HPMC as the pellet forming powders of self-emulsifying pellets, so as to achieve controlled release of drugs ( Table 1 ). For example, Zhang et al [ 60 ] developed self-emulsifying sustained release pellets of puerarin for oral bioavailability enhancement, and Tao et al [ 61 ] prepared sirolimus (SRL) self-emulsifying powder by mixing SEDDS with low viscosity HPMC grade as tabletting and sustained release aid.…”

Section: Components Of S-seddsmentioning

confidence: 99%

“…Besides pellet forming agents, adsorbents and crystallization inhibitors described above, other components in powder form—like antioxidants and disintegrants—may have to be added into S-SEDDS formulations for stability purposes. Tao et al [ 61 ] optimized S-SEDDS formulations by adding 0.20% of citric acid to increase the stability of SRL under high temperature (40 ± 2 °C), humidity (relative humidity 90 ± 5%) and strong light irradiation (4500 ± 500 lx).…”

Section: Components Of S-seddsmentioning

confidence: 99%

“…Most of the formulations contain drugs with LogP between 2 and 4 [ 23 ]. However, a considerable number of studies report S-SEDDS with drugs of quite low lipophilicity with LogP < 2 [ 46 , 50 , 51 ], which are formulated using Type III LFCS, and a considerable greater number report S-SEDDS with drugs of quite high lipophilicity with LogP > 4 [ 32 , 33 , 34 , 37 , 61 , 65 , 66 , 67 ], which are formulated using surfactant based Type IV LFCS. Most of the S-SEDDS cases presented in Table 1 pertain to solubility improvement of BCS class II drugs (67.6%) and fewer cases for the improvement of both solubility and permeability of the class IV drugs (14.7%).…”

Section: Examples Of S-sedds Formulations—instant Release and Contmentioning

confidence: 99%

“…Therefore, it is surprising that there are no S-SEDDS products yet in the market. The reasons could be related to the limited number of stability studies [ 61 ], and hence regulation issues, drug leakage and precipitation when diluted upon arrival in the GI fluids.…”

Section: Examples Of S-sedds Formulations—instant Release and Contmentioning

confidence: 99%

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Self-Emulsifying Granules and Pellets: Composition and Formation Mechanisms for Instant or Controlled Release

Nikolakakis

Partheniadis

2017

Pharmaceutics

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Many articles have been published in the last two decades demonstrating improvement in the dissolution and absorption of low solubility drugs when formulated into self-emulsifying drug delivery systems (SEDDS). Several such pharmaceutical products have appeared in the market for medium dose (Neoral® for Cyclsoprin A, Kaletra® for Lopinavir and Ritonavir), or low dose medications (Rocaltrol® for Calcitriol and Avodart® for Dutasteride). However, these are in the form of viscous liquids or semisolid presentations, characterized by the disadvantages of high production cost, stability problems and the requirement of large quantities of surfactants. Solid SEDDS (S-SEDDS), as coarse powders, granules or pellets, besides solubility improvement, can be filled easily into capsules or processed into tablets providing a handy dosage form with instant release, which can be further developed into controlled release by mixing with suitable polymers or coating with polymeric films. In this review, the materials used for the preparation of S-SEDDS, their properties and role in the formulations are detailed. Factors affecting the physical characteristics, mechanical properties of S-SEDDS as well as their in vitro release and in vivo absorption are discussed. The mechanisms involved in the formation of instant and sustained release self-emulsifying granules or pellets are elucidated. Relationships are demonstrated between the characteristics of S-SEDDS units (size, shape, mechanical properties, re-emulsification ability, drug migration and drug release) and the properties of the submicron emulsions used as massing liquids, with the aim to further elucidate the formation mechanisms. The influence of the composition of the powdered ingredients forming the granule or pellet on the properties of S-SEDDS is also examined. Examples of formulations of S-SEDDS that have been reported in the literature in the last thirteen years (2004–2017) are presented.

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Section: Components Of S-seddsmentioning

confidence: 99%

Section: Components Of S-seddsmentioning

confidence: 99%

Section: Examples Of S-sedds Formulations—instant Release and Contmentioning

confidence: 99%

Section: Examples Of S-sedds Formulations—instant Release and Contmentioning

confidence: 99%

See 2 more Smart Citations

Self-Emulsifying Granules and Pellets: Composition and Formation Mechanisms for Instant or Controlled Release

Nikolakakis

Partheniadis

2017

Pharmaceutics

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“…This tablet formulation showed good stability during storage over 3 months at 40 • C/75% RH and significantly increased oral BA and extended plasma concentration compared with the marketed Dynacirc ® capsule [254]. Tao et al prepared sirolimus self-emulsifying powder by mixing SEDDSs with MCC and a low viscosity HPMC grade as the tableting and sustained-release excipient [255]. Serratoni et al developed a controlled release pellets of methyl and propyl paraben by first incorporating them into SEDDS formulation to enhance the release rate.…”

Section: Sustained Releasementioning

confidence: 99%

Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

Park

Kim

2020

Pharmaceutics

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Self-emulsifying drug delivery systems (SEDDSs) are a vital strategy to enhance the bioavailability (BA) of formulations of poorly water-soluble compounds. However, these formulations have certain limitations, including in vivo drug precipitation, poor in vitro in vivo correlation due to a lack of predictive in vitro tests, issues in handling of liquid formulation, and physico-chemical instability of drug and/or vehicle components. To overcome these limitations, which restrict the potential usage of such systems, the supersaturable SEDDSs (su-SEDDSs) have gained attention based on the fact that the inclusion of precipitation inhibitors (PIs) within SEDDSs helps maintain drug supersaturation after dispersion and digestion in the gastrointestinal tract. This improves the BA of drugs and reduces the variability of exposure. In addition, the formulation of solid su-SEDDSs has helped to overcome disadvantages of liquid or capsule dosage form. This review article discusses, in detail, the current status of su-SEDDSs that overcome the limitations of conventional SEDDSs. It discusses the definition and range of su-SEDDSs, the principle mechanisms underlying precipitation inhibition and enhanced in vivo absorption, drug application cases, biorelevance in vitro digestion models, and the development of liquid su-SEDDSs to solid dosage forms. This review also describes the effects of various physiological factors and the potential interactions between PIs and lipid, lipase or lipid digested products on the in vivo performance of su-SEDDSs. In particular, several considerations relating to the properties of PIs are discussed from various perspectives.Pharmaceutics 2020, 12, 365 2 of 57 intraluminal supersaturation and the biorelevance of supersaturation assays will be addressed. Finally, we will make suggestions for the successful development of su-SEDDs.There are many review articles that give useful information about the nature and application of supersaturable drug delivery systems or conventional SEDDSs. However, these reviews cover only a limited range of su-SEDDSs. Therefore, this review, which includes the current status of technology focused only on su-SEDDSs, is a valuable addition to the previous review literature because no review article currently covers such a wide range of su-SEDDSs. Conventional Solubilized SEDDSsThere has been a steady increase in the number of new drug candidates (almost 40%) that are highly hydrophobic and poorly water-soluble. The oral bioavailability of poorly water-soluble drugs is hindered by low solubility and slow dissolution in the aqueous environment of the GIT. Thus, it is a great challenge for pharmaceutical scientists to overcome the inherent slow dissolution and poor oral absorption of hydrophobic drugs [1][2][3][4]. SEDDSs have emerged as a promising approach to improving the biopharmaceutical performance of hydrophobic drugs by enhancing their bioavailability [5,6].An SEDDS is a pre-concentrate composed of a drug, oils, surfactants, and sometimes co-solvents and/or co-surfactan...

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Influence of Hydroxypropylmethylcellulose and Sodium Lauryl Sulfate on the Solubility and Dissolution of Sirolimus in Solvent‐evaporated Solid Dispersions

Kim

Choi

Jin

2018

Bulletin Korean Chem Soc

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The object of this study was to investigate the influence of hydroxypropylmethylcellulose (HPMC) and sodium lauryl sulfate (SLS) on the solubility, dissolution, and crystallinity of poorly water-soluble sirolimus in solvent-evaporated solid dispersions. For the selection of suitable carriers, the influence of carriers on the solubility of sirolimus was identified. Among the carriers tested, HPMC and SLS gave most improved drug solubility, resulting in selecting them as a suitable polymer and surfactant, respectively. Numerous solvent-evaporated solid dispersions were prepared with various ratios of sirolimus, SLS, and HPMC via the spray-drying system. Then, their aqueous solubility, dissolution, and crystallinity were evaluated. All generated formulations significantly enhanced the solubility and dissolution of drug when compared with the sirolimus powder. As the amount of HPMC and SLS were increased, the solubility and dissolution in solvent-evaporated solid dispersions were increased. Moreover, all the solid dispersions represented the amorphous form of drug. Among the solid dispersions evaluated, the solid dispersion consisted of sirolimus, HPMC, and SLS at the weight ratio of 1:5:0.1 had most improved aqueous solubility (350.83 AE 11.92 vs. 0.003 AE 0.001 μg/mL) and dissolution (12.58 AE 1.31 vs. 1.13 AE 0.60%, at 240 min) compared with drug powder, respectively. This solvent-evaporated solid dispersion appeared as the round-shape and reduced the particle sizes. Thus, HPMC and SLS considerably affected the solubility and dissolution. Furthermore, this novel solvent-evaporated solid dispersion would be a potential candidate for oral preparation of sirolimus.

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Development of solidified self-microemulsifying delivery systems with enhanced stability of sirolimus and extended release

Cited by 15 publications

References 15 publications

Self-Emulsifying Granules and Pellets: Composition and Formation Mechanisms for Instant or Controlled Release

Self-Emulsifying Granules and Pellets: Composition and Formation Mechanisms for Instant or Controlled Release

Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

Influence of Hydroxypropylmethylcellulose and Sodium Lauryl Sulfate on the Solubility and Dissolution of Sirolimus in Solvent‐evaporated Solid Dispersions

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