Development, recent advances, and updates in binary, ternary co-amorphous systems, and ternary solid dispersions

Binary co-amorphous systems (CAMS) are a type of solid dispersion containing an active pharmaceutical ingredient (API) and small molecule excipients. The properties of these substances make them novel and a very demanding aspect of pharmaceutical research because they improve solubility, physical stability, and bioavailability in poorly soluble drugs in comparison to their pure crystal or amorphous counterparts. Binary CAMS may however not satisfy all criteria related to dissolution, solubility, recrystallization prevention, and stability. As a result, ternary systems incorporating a third ingredient in CAMS offer several advantages in terms of stability and drug solubility.

Similarly, ternary systems in the context of amorphous solid dispersion (ASD) improve the drug’s stability and solubility over binary solid dispersions. During this review, we summarize recent findings regarding ternary CAMS, ternary solid dispersion (TSD) and binary CAMS. Recent advances in the preparation, mechanism of stabilization, and in-vitro and in-vivo performances of binary and ternary systems are also discussed along with their final dosage forms.

Table 3

Recent studies on ternary solid dispersion (TSD) since 2016. TPGS: tocopheryl polyethylene glycol 1000 succinate, SDS: Sodium dodecyl sulfate, SLS: Sodium lauryl sulfate, HPMCP: hydroxypropyl methylcellulose phthalate, HPMC: hydroxypropyl methylcellulose, PEG: polyethylene glycol, HP-b-CD: 2-Hydroxypropyl-beta-cyclodextrin, PVP: poly vinyl pyrrolidone, HPMCAS: hypromellose acetate succinate, HME: hot melt extrusion.

Binary solid dispersion	Third ingredient	The additional ingredient’s type	Outcomes	Method
LW6 (3-[2-(4-adamantan-1-yl-phenoxy)- acetylamino]-4-hydroxy-benzoic acid methyl ester)-Povidone K30	Poloxamer 407	Polymer	Increase solubility	Solvent evaporation
Lurasidone - Poloxamer 188	Florite	Adsorbent	Inhibited transition from an amorphous to the crystalline form and enhanced stability of amorphous form.	Fusion method
Carbamazepine-Kollidon® VA64	Neusilin UFL2	Adsorbent	Enhanced the dissolution and carbamazepine flowability.	Rotary evaporation
Celecoxib -Phosphatidylcholine (PC)	Neusilin US2	Adsorbent	Improved flowability	Solvent evaporation
Itraconazole- HPMCP	Soluplus	Polymer	Increase solubility, stability and processability,	Hot melt extrusion/Spray drying
Nateglinide-Poloxamer 188	Na2CO3	pH modulator	Boosting nateglinide’s bioavailability by up to four times	melt dispersion
Abiraterone- HP-b-CD	HPMCAS	Polymer	Increase Precipitation inhibition	KinetiSol® technology
Tectorigenin- PVP	PEG4000	Polymer	Increase solubility	Rotary evaporation
Dipyridamole -Eudragit® S100	Tartaric acid	pH modulator	Rapid dissolution of dipyridamole	Freeze-drying
Glycyrrhetinic acid- PVP	l-arginine/ meglumine	pH modulator	enhance ionization, thereby increasing solubility	HME
Cinnarizine- Soluplus	HPMC/PVP	Polymer	Increase Solubility and stability	HME
Nifedipine- HPMC	Eudragit®-S	Polymer	Increase Solubility	Spray drying
Bedaquiline fumarate-Poloxamer 188	TPGS	Surfactant	Increase solubility, dissolution rate and permeability	Solvent evaporation
Ritonavir- HPMCAS	SLS	Surfactant	Inhibit recrystallization	Solvent evaporation
Loratadine-shellac	HPMC	Polymer	Increase solubility and supersaturation of loratadine	HME
Chlorthalidone -Soluplus	SLS	Surfactant	5.5 times more solubility compared with the pure drug	Spray dried
Felodipine -Soluplus	SDS	Surfactant	Increased dissolution	HME
Ezetimibe- PVP K30	Poloxamer 188	Surfactant	Improved solubility and supersaturation in the bio-relevant media.	Melt quenching

Download the full article as PDF here Development, recent advances, and updates in binary, ternary co-amorphous systems, and ternary solid dispersions

or read it here

Arezoo Saberi, Maryam Kouhjani, Davood Yari, Afsaneh Jahani, Kofi Asare-Addo, Hossein Kamali, Ali Nokhodchi,
Development, recent advances, and updates in binary, ternary co-amorphous systems, and ternary solid dispersions,
Journal of Drug Delivery Science and Technology, Volume 86, 2023, 104746, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2023.104746.