Preformulation Studies of Ezetimibe-Simvastatin Solid Dispersions in the Development of Fixed-Dose Combinations

Gòrniak, Agata; Złocińska, Adrianna; Trojan, Mateusz; Pęcak, Adrianna; Karolewicz, Bożena

doi:10.3390/pharmaceutics14050912

Cited by 8 publications

(6 citation statements)

References 55 publications

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“…Additionally, the developments in the manufacturing arena helped to identify the impact of process variables over critical quality attributes (CQA’s) of ASDs and also led to the development of novel manufacturing processes like Kinetisol ® dispersing (KSD) [ 29 ], selective laser sintering (SLS) [ 30 ] and fused deposition modeling (FDM) 3D printing [ 31 ], electronanospinning, and others [ 32 ]. It is worth mentioning the recent advancements in preformulation space, which aimed to understand the interactions between the formulation components at a molecular level [ 33 ]; this was possible through analytical techniques and molecular simulation predictions using in-silico tools [ 34 ]. Besides the advances in formulation and preformulation approaches, traditional analytical techniques such as differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) still play a major role in detecting crystallinity [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Amorphous Solid Dispersions: Preformulation, Formulation Strategies, Technological Advancements and Characterization

et al. 2022

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Amorphous solid dispersions (ASDs) are among the most popular and widely studied solubility enhancement techniques. Since their inception in the early 1960s, the formulation development of ASDs has undergone tremendous progress. For instance, the method of preparing ASDs evolved from solvent-based approaches to solvent-free methods such as hot melt extrusion and Kinetisol®. The formulation approaches have advanced from employing a single polymeric carrier to multiple carriers with plasticizers to improve the stability and performance of ASDs. Major excipient manufacturers recognized the potential of ASDs and began introducing specialty excipients ideal for formulating ASDs. In addition to traditional techniques such as differential scanning calorimeter (DSC) and X-ray crystallography, recent innovations such as nano-tomography, transmission electron microscopy (TEM), atomic force microscopy (AFM), and X-ray microscopy support a better understanding of the microstructure of ASDs. The purpose of this review is to highlight the recent advancements in the field of ASDs with respect to formulation approaches, methods of preparation, and advanced characterization techniques

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Section: Introductionmentioning

confidence: 99%

Recent Advances in Amorphous Solid Dispersions: Preformulation, Formulation Strategies, Technological Advancements and Characterization

et al. 2022

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“…Due to its apola nature and the configuration it assumes with other molecules in the membrane, PIP affec the fluidity of the cellular membrane [48]. An increase in the membrane fluidity of epithelia cells may contribute to the enhanced absorption of drugs, such as salicylates and medroxy progestrone, in epithelial and cancer cells, as demonstrated by Kajii and colleagues [48,49] Considering the mentioned above, the fact that PIP presents low toxicity in both hu mans and animals and is classified as a GRAS molecule [19], together with the point tha eutectic mixtures will not require clinical trials for its use [16,28], these results showe promising potential of pharmaceutical formulations. In addition, it would be interestin to continue studying this eutectic system by, for example, conducting toxicological tests…”

Section: Powder Dissolution Testmentioning

confidence: 99%

“…Eutectic mixtures are easily produced [24] and may offer a potentially fruitful alternative for combination therapy [16]. Furthermore, the eutectic mixtures are cost-effective, easily scaled-up, and do not require clinical trials [16,28]. Hence, the aim of this study was to obtain a eutectic mixture from SQV using PIP as a coformer to improve the dissolution of this Class II drug.…”

Section: Determination Of Mixtures Composition At the Eutectic Pointmentioning

confidence: 99%

Saquinavir-Piperine Eutectic Mixture: Preparation, Characterization, and Dissolution Profile

Fandaruff,

Quirós-Fallas,

Vega-Baudrit

et al. 2023

Pharmaceutics

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The dissolution rate of the anti-HIV drug saquinavir base (SQV), a poorly water-soluble and extremely low absolute bioavailability drug, was improved through a eutectic mixture formation approach. A screening based on a liquid-assisted grinding technique was performed using a 1:1 molar ratio of the drug and the coformers sodium saccharinate, theobromine, nicotinic acid, nicotinamide, vanillin, vanillic acid, and piperine (PIP), followed by differential scanning calorimetry (DSC). Given that SQV-PIP was the only resulting eutectic system from the screening, both the binary phase and the Tammann diagrams were adapted to this system using DSC data of mixtures prepared from 0.1 to 1.0 molar ratios in order to determine the exact eutectic composition. The SQV-PIP system formed a eutectic at a composition of 0.6 and 0.40, respectively. Then, a solid-state characterization through DSC, powder X-ray diffraction (PXRD), including small-angle X-ray scattering (SAXS) measurements to explore the small-angle region in detail, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and a powder dissolution test were performed. The conventional PXRD analyses suggested that the eutectic mixture did not exhibit structural changes; however, the small-angle region explored through the SAXS instrument revealed a change in the crystal structure of one of their components. FT-IR spectra showed no molecular interaction in the solid state. Finally, the dissolution profile of SQV in the eutectic mixture was different from the dissolution of pure SQV. After 45 min, approximately 55% of the drug in the eutectic mixture was dissolved, while, for pure SQV, 42% dissolved within this time. Hence, this study concludes that the dissolution rate of SQV can be effectively improved through the approach of using PIP as a coformer.

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“…It has a very low bioavailability of 40% due to the extensive first-pass metabolism mainly in the liver. Moreover, it shows higher intra as well as inter-subject variation, deficiency in dose proportionality, and pH-dependent solubility (3) . EZE is an ideal drug candidate to be formulated in the form of SNEDDS thereby it will enhance the aqueous solubility, protect from first-pass metabolism and increase its absorption by lymphatic transport which could improve its bioavailability (4) .…”

Section: Introductionmentioning

confidence: 99%

Solubility Enhancement of Poorly Soluble Drug Ezetimibe by Developing Self Nano Emulsifying Drug Delivery System

Doke¹,

Khutle²,

Sharma³

et al. 2022

IJST

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Objectives: To enhance solubility, dissolution, and permeability of poorly water-soluble drug Ezetimibe (EZE) using a self-nano emulsifying drug delivery system (SNEDDS). Methods: Initially, the solubility of the EZE was determined in various oils and buffers. Surfactants and co-surfactants were screened based on the solubility of the drug in oil as per the emulsification efficacy test. Liquid SNEDDS was developed and characterized. Solid SNEDDS was developed and characterized using optimized liquid SNEDDS followed by the development of EZE-loaded Tablet SNEDDS. Finding: Liquid SNEDDS (L-SNEDDS) was formulated using Capmul MCM C8 EP, Cremophore RH 40, and Labrafil M 2125 CS as oil, surfactant, and co-surfactant respectively. Optimized L-SNEDDS formulation was found to be efficient with an average %T of 99.5%, drug content of 98.43%, flask inversion 0 numbers, and the average particle size of 36.7 nm, zeta potential of -57.5 mV, Polydispersibility index in of 0.119. Also, the in vitro release profile of drug from L-SNEDDS encapsulated in hard gelatin capsules was evaluated in different dissolution media viz. simulated gastric fluid and simulated intestinal fluid. For the drug, more than 95% cumulative release was observed within 30 min exclusive of the pH of the medium. The L-SNEDDS were adsorbed on a solid support and then mixed with tablet blends and compressed into tablets. Further, no adverse changes in globule size, shape, the zeta potential of SNEDDS, and dissolution profile were apparent on conversion to solid powder form and tablet form. Novelty: The developed liquid SNEDDS form of EZE showed enhanced solubility, dissolution, and permeability in comparison to pure drugs. Conversion of L-SNEDDS to P-SNEDDS would be a novel approach to overcome the limitations associated https://www.indjst.org/ 1504

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Preformulation Studies of Ezetimibe-Simvastatin Solid Dispersions in the Development of Fixed-Dose Combinations

Cited by 8 publications

References 55 publications

Recent Advances in Amorphous Solid Dispersions: Preformulation, Formulation Strategies, Technological Advancements and Characterization

Recent Advances in Amorphous Solid Dispersions: Preformulation, Formulation Strategies, Technological Advancements and Characterization

Saquinavir-Piperine Eutectic Mixture: Preparation, Characterization, and Dissolution Profile

Solubility Enhancement of Poorly Soluble Drug Ezetimibe by Developing Self Nano Emulsifying Drug Delivery System

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