Pharmaceutical Co-crystals, Salts, and Co-amorphous Systems: A novel opportunity of hot-melt extrusion

Narala, Sagar; Nyavanandi, Dinesh; Srinivasan, Priyanka; Mandati, Preethi; Bandari, Suresh; Repka, Michael A.

doi:10.1016/j.jddst.2020.102209

Cited by 34 publications

(31 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More significantly, from a utility and healthcare perspective, the number of US-FDA-approved cocrystal drugs has been on the increase since 2015. Consequently, now the field is advancing from laboratory screening of cocrystals and polymorphs to industrial-scale production and process design challenges in the pharmaceutical industry. − ,− …”

Section: Applications Of Pharmaceutical Cocrystalsmentioning

confidence: 99%

Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs

2022

View full text Add to dashboard Cite

The subject of crystal engineering started in the 1970s with the study of topochemical reactions in the solid state. A broad chemical definition of crystal engineering was published in 1989, and the supramolecular synthon concept was proposed in 1995 followed by heterosynthons and their potential applications for the design of pharmaceutical cocrystals in 2004. This review traces the development of supramolecular synthons as robust and recurring hydrogen bond patterns for the design and construction of supramolecular architectures, notably, pharmaceutical cocrystals beginning in the early 2000s to the present time. The ability of a cocrystal between an active pharmaceutical ingredient (API) and a pharmaceutically acceptable coformer to systematically tune the physicochemical properties of a drug (i.e., solubility, permeability, hydration, color, compaction, tableting, bioavailability) without changing its molecular structure is the hallmark of the pharmaceutical cocrystals platform, as a bridge between drug discovery and pharmaceutical development. With the design of cocrystals via heterosynthons and prototype case studies to improve drug solubility in place (2000–2015), the period between 2015 to the present time has witnessed the launch of several salt–cocrystal drugs with improved efficacy and high bioavailability. This review on the design, synthesis, and applications of pharmaceutical cocrystals to afford improved drug products and drug substances will interest researchers in crystal engineering, supramolecular chemistry, medicinal chemistry, process development, and pharmaceutical and materials sciences. The scale-up of drug cocrystals and salts using continuous manufacturing technologies provides high-value pharmaceuticals with economic and environmental benefits.

show abstract

Section: Applications Of Pharmaceutical Cocrystalsmentioning

confidence: 99%

Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs

2022

View full text Add to dashboard Cite

show abstract

“…Substantial interest has thus been provided to the study of novel approaches aimed at enhancing the bioavailability of drugs, especially those capable of increasing drug solubility [ 6 , 7 , 8 , 9 , 10 , 11 ]. Among these, the preparation and stabilization of amorphous drugs using low molecular weight compounds—producing co-amorphous systems (CAMs)—has been considered a viable strategy, resulting in a suitable compromise between solubility improvement and stability in the amorphous form [ 8 , 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…Concomitantly, other unit operations, such as tableting, have also proved to be effective in the preparation of amorphous materials [ 19 , 20 ]. To date, a notable endeavor has been put into the development of CAMs, namely on the selection of the co-formers [ 13 , 21 , 22 , 23 ], the adequate drug: co-former molar ratio [ 24 ] and CAM preparation methods [ 11 , 25 , 26 ]. However, the formulation of CAMs in oral solid dosage forms (e.g., tablets) has been barely described [ 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends

et al. 2022

View full text Add to dashboard Cite

The work evaluates the stability of amorphous and co-amorphous olanzapine (OLZ) in tablets manufactured by direct compression. The flowability and the compressibility of amorphous and co-amorphous OLZ with saccharin (SAC) and the properties of the tablets obtained were measured and compared to those of tablets made with crystalline OLZ. The flowability of the amorphous and mostly of the co-amorphous OLZ powders decreased in comparison with the crystalline OLZ due to the higher cohesiveness of the former materials. The stability of the amorphous and co-amorphous OLZ prior to and after tableting was monitored by XRPD, FTIR, and NIR spectroscopies. Tablets presented long-lasting amorphous OLZ with enhanced water solubility, but the release rate of the drug decreased in comparison with tablets containing crystalline OLZ. In physical mixtures made of crystalline OLZ and SAC, an extent of amorphization of approximately 20% was accomplished through the application of compaction pressures and dwell times of 155 MPa and 5 min, respectively. The work highlighted the stability of amorphous and co-amorphous OLZ during tableting and the positive effect of compaction pressure on the formation of co-amorphous OLZ, providing an expedited amorphization technique, given that the process development-associated hurdles were overcome.

show abstract

“…Hot-melt extrusion (HME) is one such method of synthesizing cocrystals through temperature controlled, mechanochemical grinding [ 26 , 27 , 28 ]. HME is a novel technique adopted from the plastic and polymer industries.…”

Section: Introductionmentioning

confidence: 99%

“…New hydrogen bonds will form between complementary pairs during the conveying stage of the HME process and during cooling, forming cocrystals [ 6 , 25 , 27 ]. Over the last decade, HME has received renewed attention in the pharmaceutical industry as it offers distinct advantages over other commercially available pharmaceutical processing technique [ 26 ]. Some of these advantages include the fact it is a solvent-free non-ambient process; is economical offering a reduced production time and having fewer processing steps when compared to other techniques; it is a continuous process; extrudes products in a uniform shape; quality assurance can be easily monitored through process analytical technology (PAT) and that HME has been shown to increases the solubility and bioavailability of insoluble compounds when compared to other processing techniques [ 30 , 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Continuous Manufacture and Scale-Up of Theophylline-Nicotinamide Cocrystals

et al. 2021

View full text Add to dashboard Cite

The aim of the study was the manufacturing and scale-up of theophylline-nicotinamide (THL-NIC) pharmaceutical cocrystals processed by hot-melt extrusion (HME). The barrel temperature profile, feed rate and screw speed were found to be the critical processing parameters with a residence time of approximately 47 s for the scaled-up batches. Physicochemical characterization using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction of bulk and extruded materials revealed the formation of high purity cocrystals (98.6%). The quality of THL-NIC remained unchanged under accelerated stability conditions.

show abstract

Pharmaceutical Co-crystals, Salts, and Co-amorphous Systems: A novel opportunity of hot-melt extrusion

Cited by 34 publications

References 100 publications

Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs

Crystal Engineering of Pharmaceutical Cocrystals in the Discovery and Development of Improved Drugs

Downstream Processing of Amorphous and Co-Amorphous Olanzapine Powder Blends

Continuous Manufacture and Scale-Up of Theophylline-Nicotinamide Cocrystals

Contact Info

Product

Resources

About