Ternary Solid Dispersion Strategy for Solubility Enhancement of Poorly Soluble Drugs by Co-Milling Technique

Béjaoui, M.; Oueslati, H.; Galai, Haykel

doi:10.5772/intechopen.95518

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…It is a clear possibility that transforming from crystalline state to amorphous state by dry milling can happen [ 60 , 61 ]. Co-milling with PVP is the method of preparing amorphous solid dispersion, and it is expected that there exist no melting peaks in amorphous state.…”

Section: Resultsmentioning

confidence: 99%

Celecoxib Nanoformulations with Enhanced Solubility, Dissolution Rate, and Oral Bioavailability: Experimental Approaches over In Vitro/In Vivo Evaluation

et al. 2023

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Celecoxib (CXB) is a Biopharmaceutical Classification System (BCS) Class II molecule with high permeability that is practically insoluble in water. Because of the poor water solubility, there is a wide range of absorption and limited bioavailability following oral administration. These unfavorable properties can be improved using dry co-milling technology, which is an industrial applicable technology. The purpose of this study was to develop and optimize CXB nanoformulations prepared by dry co-milling technology, with a quality by design approach to maintain enhanced solubility, dissolution rate, and oral bioavailability. The resulting co-milled CXB composition using povidone (PVP), mannitol (MAN) and sodium lauryl sulfate (SLS) showed the maximum solubility and dissolution rate in physiologically relevant media. Potential risk factors were determined with an Ishikawa diagram, important risk factors were selected with Plackett-Burman experimental design, and CXB compositions were optimized with Central Composite design (CCD) and Bayesian optimization (BO). Physical characterization, intrinsic dissolution rate, solubility, and stability experiments were used to evaluate the optimized co-milled CXB compositions. Dissolution and permeability studies were carried out for the resulting CXB nanoformulation. Oral pharmacokinetic studies of the CXB nanoformulation and reference product were performed in rats. The results of in vitro and in vivo studies show that the CXB nanoformulations have enhanced solubility (over 4.8-fold (8.6 ± 1.06 µg/mL vs. 1.8 ± 0.33 µg/mL) in water when compared with celecoxib pure powder), and dissolution rate (at least 85% of celecoxib is dissolved in 20 min), and improved oral pharmacokinetic profile (the relative bioavailability was 145.2%, compared to that of Celebrex®, and faster tmax 3.80 ± 2.28 h vs. 6.00 ± 3.67 h, indicating a more rapid absorption rate).

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Section: Resultsmentioning

confidence: 99%

Celecoxib Nanoformulations with Enhanced Solubility, Dissolution Rate, and Oral Bioavailability: Experimental Approaches over In Vitro/In Vivo Evaluation

et al. 2023

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“…of efavirenz was successfully obtained by ternary solid dispersion using PVP and polyethylene glycol 8000 [61]. In addition to aforesaid, we have recently reported that solubility enhancement of poorly soluble drugs can be achieved by co-milling the drug in the presence of multiple carriers, and led to the formation of physically stable amorphous system and was more effective than simple binary systems [62].…”

Section: Dosage Formsmentioning

confidence: 99%

Multifunctional Roles of PVP as a Versatile Biomaterial in Solid State

Béjaoui¹,

Galai²,

Touati³

et al. 2023

Dosage Forms - Innovation and Future Perspectives

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Polyvinylpyrrolidone (PVP) has proven to be a highly versatile material, as evidenced by its long history as multifunctional biomaterial with a wide range of high-performance applications (e.g., tissue engineering, drug delivery systems, and ophthalmologic applications). PVP was frequently used in medical and pharmaceutical field due to its several interesting properties (higher glass transition temperature, water solubility, biocompatibility, biodegradability, chemical stability, very good adhesive, and emulsifying agent). This chapter highlights the multifunctional roles of PVP in pharmaceutical formulations in solid state. In fact, PVP acted as a stabilizing agent for various amorphous drug molecules by minimizing their molecular mobility. Physical stabilization resulted from the reinforcement of intermolecular interactions in binary or ternary systems due to the synergetic effect of PVP. This made it possible to overcome several challenges for drug formulations (e.g., solubility and bioavailability weakness, physical instability under stress conditions, complexation efficiency of cyclodextrin molecules). In this chapter, the effect of PVP on the binary solid dispersion (indomethacin:kaolin) is discussed. We have shown that PVP enhanced physical stability of amorphous indomethacin under stress conditions (at RH: 75% and T = 40°C for three months), leading to the improvement of drug aqueous solubility by suppressing kaolin adsorption effect.

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“…Furthermore, the dissolution rate of ibuprofen was significantly increased in the presence of PVP and complexation by βCD. This was due to various mechanisms (intermolecular interactions, carrier synergy, anti-plasticizing effect, increased hydrophilicity, decreased particle size, and accretion to βCD cavities) that promote the stabilization of amorphous ibuprofen under stress conditions [ 120 ].…”

Section: Physical Stabilitymentioning

confidence: 99%

Ternary Solid Dispersions: A Review of the Preparation, Characterization, Mechanism of Drug Release, and Physical Stability

Budiman,

Lailasari,

Nurani

et al. 2023

Pharmaceutics

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The prevalence of active pharmaceutical ingredients (APIs) with low water solubility has experienced a significant increase in recent years. These APIs present challenges in formulation, particularly for oral dosage forms, despite their considerable therapeutic potential. Therefore, the improvement of solubility has become a major concern for pharmaceutical enterprises to increase the bioavailability of APIs. A promising formulation approach that can effectively improve the dissolution profile and the bioavailability of poorly water-soluble drugs is the utilization of amorphous systems. Numerous formulation methods have been developed to enhance poorly water-soluble drugs through amorphization systems, including co-amorphous formulations, amorphous solid dispersions (ASDs), and the use of mesoporous silica as a carrier. Furthermore, the successful enhancement of certain drugs with poor aqueous solubility through amorphization has led to their incorporation into various commercially available preparations, such as ASDs, where the crystalline structure of APIs is transformed into an amorphous state within a hydrophilic matrix. A novel approach, known as ternary solid dispersions (TSDs), has emerged to address the solubility and bioavailability challenges associated with amorphous drugs. Meanwhile, the introduction of a third component in the ASD and co-amorphous systems has demonstrated the potential to improve performance in terms of solubility, physical stability, and processability. This comprehensive review discusses the preparation and characterization of poorly water-soluble drugs in ternary solid dispersions and their mechanisms of drug release and physical stability.

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Ternary Solid Dispersion Strategy for Solubility Enhancement of Poorly Soluble Drugs by Co-Milling Technique

Cited by 4 publications

References 36 publications

Celecoxib Nanoformulations with Enhanced Solubility, Dissolution Rate, and Oral Bioavailability: Experimental Approaches over In Vitro/In Vivo Evaluation

Celecoxib Nanoformulations with Enhanced Solubility, Dissolution Rate, and Oral Bioavailability: Experimental Approaches over In Vitro/In Vivo Evaluation

Multifunctional Roles of PVP as a Versatile Biomaterial in Solid State

Ternary Solid Dispersions: A Review of the Preparation, Characterization, Mechanism of Drug Release, and Physical Stability

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