Relationships Between the Properties of Self-Emulsifying Pellets and of the Emulsions Used as Massing Liquids for Their Preparation

Nikolakakis, Ioannis; Panagopoulou, Athanasia; Salis, A.; Malamataris, S.

doi:10.1208/s12249-014-0214-8

Cited by 8 publications

(20 citation statements)

References 31 publications

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“…Type IV surfactant based LFCS, are more suitable for filling into a capsule, in preference to formulating into self-emulsifying granules or pellets, due to the increased viscosity and the tendency to form gel when mixed with water. That is because of their viscous texture that hampers mixing and distribution into the powder components [ 15 , 31 ]. However, the introduction of new water dispersible surfactants of mono-, di- and triglycerides of polyethylene glycol esters of fatty acids [ 32 , 33 , 34 , 35 ] and the use of hydrophilic mixtures with lipophilic surfactants have made the conversion of Type IV LFCS into granules and pellets by extrusion/spheronization feasible [ 36 , 37 , 38 ].…”

Section: Solid Self-emulsifying Drug Delivery Systems (S-sedds)mentioning

confidence: 99%

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: Solid Self-emulsifying Drug Delivery Systems (S-sedds)mentioning

confidence: 99%

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

Nikolakakis

Partheniadis

2017

Pharmaceutics

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“…after removal of any suspended solid particles, shows only marginal change with time. This has not been the case for SEPs prepared with MCC only (without CSD) [34], where the decrease of T% with time was not influenced by centrifugation. Therefore, in the present SEPs composition the redispersed matter contains some CSD, probably positioned in the SEDDS liquid crystal structure.…”

Section: Reconstitution Of Emulsions From Sepsmentioning

confidence: 85%

“…From Table 4 it can be seen that the viscosity of the drug-loaded sonicated emulsion is much lower than the non-sonicated (68.5 cP compared to 249.5 cP). This indicates efficiency of the applied sonication, resulting in smooth texture and greater fluidity, which is important for efficient mixing with the solid pellet components and formation of extrudable paste [34]. Figure 2 presents the distributions of hydrodynamic diameter for sonicated and non-sonicated nanoemulsions.…”

Section: Rheologymentioning

confidence: 99%

“…The values of the untreated and sonicated emulsions were found to be negative -7.98 mV and -7.05 mV, respectively (Table 4), which may be ascribed to the presence of free fatty acids. However, this value is rather low to contribute significantly to the stability of the emulsion [19,34]. Figure 3 presents profiles of back scattering (%) vs distance for emulsions at rest.…”

Section: Droplet Size and Zeta Potentialmentioning

confidence: 99%

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Development and Permeability Testing of Self-Emulsifying Atorvastatin Calcium Pellets and Tablets of Compressed Pellets

et al. 2019

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Self-emulsifying pellets (SEPs) of Atorvastatin Calcium (AtrCa) were developed and processed into tablets (SETs). Self-emulsifying drug delivery system (SEDDS) composed of oleic acid, Tween 20, Span 80 and N-Methyl-2-pyrolidone gave great solubility improvement and was used as oil in water emulsion for the preparation of SEPs. Due to the high 60% w/w SEDDS content required to achieve a therapeutic dose in the final tablet form, sonication was necessary to improve fluidity and stability. Colloidal silicon dioxide (CSD) and microcrystalline cellulose (MCC) were the solids in the pellet formulation employed at a ratio 7:3, which enabled production of pellets with high SEDDS content and acceptable friability as well. Emulsions were characterized physico-chemically, SEPs for physical properties and reconstitution, and tablets of compressed pellets for mechanical strength, disintegration into pellets and drug release. SEPs compressed with 30% MCC at 60 MPa gave tablets of adequate strength that disintegrated rapidly into pellets within 1 min. Emulsion reconstitution took longer than drug release due to adsorption of SEDDS on CSD, implying dissolution at the pellet surface in parallel to that from the dispersed droplets. Compared to the commercial tablet, drug release from the self-emulsifying forms was faster at pH 1.2 where the drug solubility is poor, but slower at pH 6.8 where the solubility is higher. Permeability and cytotoxicity were also studied using Caco-2 cells. The results showed that drug transport from the apical to basolateral compartment of the test well was 1.27 times greater for SEPs than commercial tablets, but 0.86 times lower in the opposite direction. Statistical analysis confirmed the significance of these results. Toxicity was slightly reduced. Therefore, the increased permeability in conjunction with the protection of the drug being dissolved in the SEDDS droplets, may reduce the overall effect of presystemic metabolism and enhance bioavailability.

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“…For the improving sphericity and size uniformity of granules and pellets containing su-SEDDS, the liquid su-SEDDS should be uniformly distributed in the solidified formulation and proper mechanical strength and flowability should be ensured [235,236]. Agarwal et al showed that the important factors that can determine the physical properties of self-emulsifying powder such as flowability are particle size, specific surface area, and the type and amount of solidification excipient [237].…”

Section: Powder and Granulesmentioning

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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Relationships Between the Properties of Self-Emulsifying Pellets and of the Emulsions Used as Massing Liquids for Their Preparation

Cited by 8 publications

References 31 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

Development and Permeability Testing of Self-Emulsifying Atorvastatin Calcium Pellets and Tablets of Compressed Pellets

Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

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