Whilst monotherapy is traditionally the preferred treatment starting point for chronic conditions such as hypertension and diabetes, other diseases require the use of multiple drugs (polytherapy) from the onset of treatment (e.g., human immunodeficiency virus acquired immunodeficiency syndrome, tuberculosis, and malaria). Successful treatment of these chronic conditions is sometimes hampered by patient non-adherence to polytherapy. The options available for polytherapy are either the sequential addition of individual drug products to deliver an effective multi-drug regimen or the use of a single fixed-dose combination (FDC) therapy product. This article intends to critically review the use of FDC drug therapy and provide an insight into FDC products which are already commercially available. Shortcomings of FDC formulations are discussed from multiple perspectives and research gaps are identified. Moreover, an overview of fundamental formulation considerations is provided to aid formulation scientists in the design and development of new FDC products.

Polysaccharide rich gums and mucilages are produced by different natural sources such as plants, animals and microbial organisms to fulfil structural and physiological functions. Their diverse structural compositions with a broad range of physicochemical properties make them useful for inclusion in dosage forms for different purposes such as to improve manufacturing processes and/or to facilitate drug delivery. A number of natural gums and mucilages have been investigated for inclusion in pharmaceutical formulations for a variety of reasons. The search for new excipients continues to be an active topic in dosage form design and drug delivery research. The aim of this review article is to give an overview of the chemical nature of natural gums and mucilages and to discuss their applications in the formulation of pharmaceutical dosage forms. Special emphasis will be placed on the use of gums and mucilages in novel drug delivery systems, such as modified release dosage forms and delivery systems that target specific sites of delivery.

Multiple-unit pellet systems (MUPS) provide several pharmacokinetic and pharmacodynamic advantages over single-unit dosage forms, however, compression of pellets into MUPS tablets present certain challenges. Although the SeDeM Expert Diagram System (SeDeM EDS) was originally developed to provide information about the most appropriate excipient and the minimum amount thereof that is required for producing direct compressible tablets, this study investigated the possibility to apply the SeDeM EDS in the production of MUPS tablets. In addition, the effect of pellet size (i.e. 0.5, 1.0, 1.5, 2.0, and 2.5 mm) on SeDeM EDS predictions regarding the MUPS tablet formulations was investigated. The compressibility incidence factor values were below the acceptable value (i.e. 5.00) for all the pellet sizes. Kollidon^® VA 64 was identified as the most appropriate excipient to improve compressibility. The compression indices, namely, the parameter index (IP), parametric profile index (IPP), and good compression index (GCI) indicated that acceptable MUPS tablets could be produced from the final pellet-excipient blends based on predictions from the SeDeM EDS. These MUPS tablets complied with specifications for friability, hardness, and mass variation. The SeDeM EDS system is therefore applicable to assist in the formulation of acceptable MUPS tablets.

The SeDeM Expert Diagram System (SeDeM EDS) was originally developed to provide information about the suitability of powders to produce direct compressible tablets. Multiple-unit pellet systems (MUPS) are dosage forms consisting of pellets compressed into tablets or loaded into hard gelatin capsules. The aim of this study was to apply the SeDeM EDS to different size pellets (i.e. 0.5, 1.0, 1.5, 2.0, and 2.5 mm) containing different APIs (i.e. doxylamine, ibuprofen or paracetamol) to determine which properties should be corrected to yield MUPS tablet formulations. The SeDeM parameter tests were conducted on the pellets, selected excipients, intermediate blends, and final blends. The study showed that the properties of the pellets depended on the active ingredient and pellet size. The SeDeM compressibility indices indicated that the final pellet blends should be suitable for compression into MUPS tablets. MUPS tablets were prepared from the final blends and evaluated in terms of physico-chemical properties and dissolution profiles. Only three of the MUPS tablet formulations containing ibuprofen and one MUPS tablet formulation containing paracetamol failed content uniformity. The water solubility of the APIs as well as the pellet size (surface area exposed to the dissolution medium) attributed to the difference in drug dissolution rate.

Aloe vera gel and whole leaf materials, as well as polysaccharides, precipitated from the gel, have previously been shown to enhance macromolecular drug delivery across epithelial tissues. This study investigated the effectiveness of microparticle formulations prepared from A. vera polysaccharides for nasal delivery of insulin across excised sheep olfactory and respiratory nasal epithelial tissues. An emulsion-solvent evaporation technique was used to prepare two insulin microparticle formulations, namely one containing Eudragit^® L100 and A. vera polysaccharides and one containing A. vera polysaccharides only. In addition, an ionic gelation technique was used to prepare an insulin microparticle formulation with A. vera polysaccharides, where calcium chloride was used as a cross-linker. The microparticle formulations were evaluated in terms of drug content (assay), particle size, drug release (dissolution), ex vivo drug permeation, and histology. The microparticle formulations exhibited statistically significantly higher insulin delivery across excised sheep olfactory and respiratory nasal epithelial tissues compared to that of the control group (insulin alone). In conclusion, the use of A. vera polysaccharides in microparticle formulations significantly improved nasal insulin delivery. Therefore, A. vera polysaccharide containing microparticles showed high potential to enhance systemic bioavailability and delivery into the brain of macromolecular drugs such as insulin after intranasal administration.