The amorphous solid state offers an improved apparent solubility and dissolution rate. However, due to thermodynamic instability and recrystallization tendencies during processing, storage and dissolution, their potential application is limited. For this reason, the production of amorphous drugs with adequate stability remains a major challenge and formulation strategies based on solid molecular dispersions are being exploited. Co-amorphous systems are a new formulation approach where the amorphous drug is stabilized through strong intermolecular interactions by a low molecular co-former. This review covers several topics applicable to co-amorphous drug delivery systems. In particular, it describes recent advances in the co-amorphous composition, preparation and solid-state characterization, as well as improvements of dissolution performance and absorption are detailed. Examples of drug-drug, drug-carboxylic acid and drug-amino acid co-amorphous dispersions interacting via hydrogen bonding, π−π interactions and ionic forces, are presented together with corresponding final dosage forms.
1 May 2013 in European Journal of Pharmaceutics and Biopharmaceutics
Electrospinning (ES) is a convenient and versatile method for the fabrication of nanofibers and has been utilized in many fields including pharmaceutical and biomedical applications. Conventional ES uses a needle spinneret for the generation of nanofibers and is associated with many limitations and drawbacks (i.e., needle clogging, limited production capacity, and low yield). Needleless electrospinning (NLES) has been proposed to overcome these problems. Within the last two decades (2004–2020), many research articles have been published reporting the use of NLES for the fabrication of polymeric nanofibers intended for drug delivery and biomedical tissue engineering applications. The objective of the present mini-review article is to elucidate the potential of NLES for designing such novel nanofibrous drug delivery systems and tissue engineering constructs. This paper also gives an overview of the key NLES approaches, including the most recently introduced NLES method: ultrasound-enhanced electrospinning (USES). The technologies underlying NLES systems and an evaluation of electrospun nanofibers are presented. Even though NLES is a promising approach for the industrial production of nanofibers, it is a multivariate process, and more research work is needed to elucidate its full potential and limitations.
Nanoparticle-based therapeutics have been used in pulmonary formulations to enhance delivery of poorly water-soluble drugs, protect drugs against degradation and achieve modified release and drug targeting. This review focuses on the use of spray drying as a solidification technique to produce microparticles containing nanoparticles (i.e., nanoparticle (NP) agglomerates) with suitable properties as dry powders for inhalation. The review covers the general aspects of pulmonary drug delivery with emphasis on nanoparticle-based dry powders for inhalation and the principles of spray drying as a method for the conversion of nanosuspensions to microparticles. The production and therapeutic applications of the following types of NP agglomerates are presented: nanoporous microparticles, nanocrystalline agglomerates, lipid-based and polymeric formulations. The use of alternative spray-drying techniques, namely nano spray drying, and supercritical CO2-assisted spray drying is also discussed as a way to produce inhalable NP agglomerates.
Many articles have been published in the last two decades demonstrating improvement in the dissolution and absorption of low solubility drugs when formulated into self-emulsifying drug delivery systems (SEDDS). Several such pharmaceutical products have appeared in the market for medium dose (Neoral® for Cyclsoprin A, Kaletra® for Lopinavir and Ritonavir), or low dose medications (Rocaltrol® for Calcitriol and Avodart® for Dutasteride). However, these are in the form of viscous liquids or semisolid presentations, characterized by the disadvantages of high production cost, stability problems and the requirement of large quantities of surfactants. Solid SEDDS (S-SEDDS), as coarse powders, granules or pellets, besides solubility improvement, can be filled easily into capsules or processed into tablets providing a handy dosage form with instant release, which can be further developed into controlled release by mixing with suitable polymers or coating with polymeric films. In this review, the materials used for the preparation of S-SEDDS, their properties and role in the formulations are detailed. Factors affecting the physical characteristics, mechanical properties of S-SEDDS as well as their in vitro release and in vivo absorption are discussed. The mechanisms involved in the formation of instant and sustained release self-emulsifying granules or pellets are elucidated. Relationships are demonstrated between the characteristics of S-SEDDS units (size, shape, mechanical properties, re-emulsification ability, drug migration and drug release) and the properties of the submicron emulsions used as massing liquids, with the aim to further elucidate the formation mechanisms. The influence of the composition of the powdered ingredients forming the granule or pellet on the properties of S-SEDDS is also examined. Examples of formulations of S-SEDDS that have been reported in the literature in the last thirteen years (2004–2017) are presented.