Anomalous dissolution behaviour of tablets prepared from sugar glass-based solid dispersions

Drooge, Dirk Jan van; Hinrichs, Wouter L. J.; Frijlink, Henderik W.

doi:10.1016/j.jconrel.2004.03.018

Cited by 76 publications

(29 citation statements)

References 31 publications

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“…5) showed approximately 94% drug was released at the end of 5 h for FBT SLN formulation (PB 9) and 62% for the marketed micronized FBT formulation at the end of 5 h, whereas 41% drug was released from pure FBT at the end of 5 h. The increase of the dissolution rate of SLN FBT could be mainly attributed to the obvious reduction of the particle size (from a few microns for the crude FBT and marketed micronized formulation to a few nanometers (125 nm) for SLN). According to NernstNoyes-Whitney equation, which described the dissolution rate of drug in a diffusion-controlled process, an increase in the surface area could result in an increase in dissolution rate [28][29][30][31].…”

Section: Quantification Of Drug Release In Vitromentioning

confidence: 99%

Continuous Production of Fenofibrate Solid Lipid Nanoparticles by Hot-Melt Extrusion Technology: a Systematic Study Based on a Quality by Design Approach

Patil

Feng

et al. 2014

AAPS J

104

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Abstract. This contribution describes a continuous process for the production of solid lipid nanoparticles (SLN) as drug-carrier systems via hot-melt extrusion (HME). Presently, HME technology has not been used for the manufacturing of SLN. Generally, SLN are prepared as a batch process, which is time consuming and may result in variability of end-product quality attributes. In this study, using Quality by Design (QbD) principles, we were able to achieve continuous production of SLN by combining two processes: HME technology for melt-emulsification and high-pressure homogenization (HPH) for size reduction. Fenofibrate (FBT), a poorly water-soluble model drug, was incorporated into SLN using HME-HPH methods. The developed novel platform demonstrated better process control and size reduction compared to the conventional process of hot homogenization (batch process). Varying the process parameters enabled the production of SLN below 200 nm. The dissolution profile of the FBT SLN prepared by the novel HME-HPH method was faster than that of the crude FBT and a micronized marketed FBT formulation. At the end of a 5-h in vitro dissolution study, a SLN formulation released 92-93% of drug, whereas drug release was approximately 65 and 45% for the marketed micronized formulation and crude drug, respectively. Also, pharmacokinetic study results demonstrated a statistical increase in Cmax, Tmax, and AUC 0-24 h in the rate of drug absorption from SLN formulations as compared to the crude drug and marketed micronized formulation. In summary, the present study demonstrated the potential use of hot-melt extrusion technology for continuous and large-scale production of SLN.

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Section: Quantification Of Drug Release In Vitromentioning

confidence: 99%

Continuous Production of Fenofibrate Solid Lipid Nanoparticles by Hot-Melt Extrusion Technology: a Systematic Study Based on a Quality by Design Approach

Patil

Feng

et al. 2014

AAPS J

104

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“…These systems consist of amorphous carriers and the drug can be either molecularly dispersed or form an amorphous precipitate into its carrier, which can possibly crystallize upon time. Examples of carriers that favour the formation of glass solutions are sugars, such as dextrose, fructose, galactose, trehalose, sucrose, and different types of inulin, [53][54][55] or amorphous polymers such as PVP, Polyvinylpyrrolidone-co-vinylacetate (PVPVA) and HPMC. The earliest examples of such glassy dispersions were prepared with PVP [56] and currently this class represents the most intensively studied and applied solid dispersion system.…”

Section: Glass Solutionsmentioning

confidence: 99%

Review: physical chemistry of solid dispersions

2009

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Objectives With poorly soluble drug candidates emerging in the drug discovery pipeline, the importance of the solid dispersion formulation approach is increasing. This strategy includes complete removal of drug crystallinity, and molecular dispersion of the poorly soluble compound in a hydrophilic polymeric carrier. The potential of this technique to increase oral absorption and hence bioavailability is enormous. Nevertheless, some issues have to be considered regarding thermodynamic instability, as well in supersaturated solutions that are formed upon dissolution as in the solid state. Key findings After a brief discussion on the historical background of solid dispersions and their current role in formulation, an overview will be given on the physical chemistry and stability of glass solutions as they form supersaturated solutions, and during their shelf life. Conclusions Thorough understanding of these aspects will elicit conscious evaluation of carrier properties and eventually facilitate rational excipient selection. Thus, full exploitation of the solid dispersion strategy may provide an appropriate answer to drug attrition due to low aqueous solubility in later stages of development.

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“…Various carriers have been used to prepare solid dispersions, and sugars are one such carrier. The sugars investigated for the preparation of solid dispersions include lactose for nitrazepam (12) and sucrose, trehalose, and two oligofructoses (inulin DP11 and inulin DP23 having number-average degrees of polymerization of 11 and 23, respectively) for diazepam (13). Similarly, mannitol, lactose, and galactose have been investigated for carbamazepine (12).…”

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confidence: 99%

Dissolution Behavior and Thermodynamic Stability of Fused-Sugar Dispersions of a Poorly Water-Soluble Drug

Singh¹,

Chhabra²,

Pathak³

2011

Dissolution Technol.

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The current research was undertaken to develop and evaluate dissolution profiles of thermodynamically stabilized sugar dispersions of the poorly water-soluble, model drug etoricoxib (ETX). Fused-sugar dispersions were formulated using sorbitol, xylitol, and maltose separately, and the binary systems were stabilized by incorporation of the antiplasticizing agents poloxamer 407 and PVP K30 to obtain ternary and quaternary systems. The sugar dispersions (F1-F12) were subjected to in vitro dissolution studies, and based on model-independent dissolution parameters, ETX-sorbitol binary/ ternary/composite systems were selected for thermodynamic stability study. The aged ETX-sorbitol composite dispersion (SF8) displayed the highest percent dissolution efficiency (%DE 80min of 78.48), the minimum t 50% of 4.45 min, and the least tendency to recrystallize (D cryst of 0.68), confirming maximum amorphization and thermodynamic stability among all the composite dispersions. The SEM photomicrographs reveal complete miscibility of drug in the aged quaternary dispersion SF8, and its diffuse reflectance (DR) spectrum confirms the absence of any chemical change. Conclusively, sorbitol binary systems can be effectively stabilized by incorporation of PVP K30-poloxamer 407 and retain the dissolution characteristics of sugar dispersions upon aging.

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Anomalous dissolution behaviour of tablets prepared from sugar glass-based solid dispersions

Cited by 76 publications

References 31 publications

Continuous Production of Fenofibrate Solid Lipid Nanoparticles by Hot-Melt Extrusion Technology: a Systematic Study Based on a Quality by Design Approach

Continuous Production of Fenofibrate Solid Lipid Nanoparticles by Hot-Melt Extrusion Technology: a Systematic Study Based on a Quality by Design Approach

Review: physical chemistry of solid dispersions

Dissolution Behavior and Thermodynamic Stability of Fused-Sugar Dispersions of a Poorly Water-Soluble Drug

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