Fixed-Dose Combination Formulations in Solid Oral Drug Therapy: Advantages, Limitations, and Design Features.

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).

Formulation of Chitosan Microparticles for Enhanced Intranasal Macromolecular Compound Delivery: Factors That Influence Particle Size during Ionic Gelation.

Therapeutic macromolecules (e.g., protein and peptide drugs) present bioavailability challenges via extravascular administration.

Comparison of RPMI 2650 cell layers and excised sheep nasal epithelial tissues in terms of nasal drug delivery and immunocytochemistry properties.

Nasal drug administration has been identified as a potential alternative to oral drug administration, especially for systemic delivery of large molecular weight compounds. Major advantages of nasal drug delivery include high vascularity and permeability of the epithelial membranes as well as circumvention of first-pass metabolism. RPMI 2650 cell layers (in vitro cell model) and excised sheep nasal mucosal tissues (ex vivo sheep model) were evaluated with regard to epithelial thickness, selected tight junction protein expression (i.

Molecular mechanisms and associated cell signalling pathways underlying the anticancer properties of phytochemical compounds from species (Review).

Naturally occurring components from various species of have been used as traditional folk medicine since the ancient times. Over the last few decades, the therapeutic effects of extracts and phytochemical compounds obtained from have been proven in preclinical and clinical studies. Recently, compounds from other species apart from have been investigated for the treatment of different diseases, with a particular focus on cancer.

Formulation of Medicated Chewing Gum Containing Sceletium tortuosum and Process Optimization Utilizing the SeDeM Diagram Expert System.

Sceletium tortuosum is one of the most promising medicinal plant species for treating anxiety and depression. Traditionally, aerial parts are chewed (masticatory herbal medicine) providing fast relief and rendering the masticatory route for delivery, ideal. This study intended formulating novel medicated chewing gum containing S.

Physicochemical Stability of Enriched Phenolic Fractions of Cyclopia genistoides and ex vivo Bi-directional Permeability of Major Xanthones and Benzophenones.

Fractions of an ultrafiltered extract, respectively enriched in xanthones and benzophenones, were previously shown to inhibit mammalian -glucosidase The present study investigated intestinal transport of these fractions, using excised porcine jejunal tissue, to determine whether the gut could be a predominant site of action. The major bioactive compounds, the xanthones (mangiferin, isomangiferin) and benzophenones (3--D-glucopyranosyliriflophenone, 3--D-glucopyranosyl-4---D-glucopyranosyliriflophenone) exhibited poor permeation in the absorptive direction with a relatively high efflux ratio (efflux ratio > 1). The efflux ratio of 3--D-glucopyranosyl-4---D-glucopyranosyliriflophenone (3.

Models used to screen for the treatment of multidrug resistant cancer facilitated by transporter-based efflux.

Purpose: Efflux transporters of the adenosine triphosphate-binding cassette (ABC)-superfamily play an important role in the development of multidrug resistance (multidrug resistant; MDR) in cancer. The overexpression of these transporters can directly contribute to the failure of chemotherapeutic drugs. Several in vitro and in vivo models exist to screen for the efficacy of chemotherapeutic drugs against MDR cancer, specifically facilitated by efflux transporters.

A sub-chronic Xysmalobium undulatum hepatotoxicity investigation in HepG2/C3A spheroid cultures compared to an in vivo model.

Ethnopharmacology Relevance: Traditional herbal medicines are utilized by 27 million South Africans. Xysmalobium undulatum (Uzara) is one of the most widely used traditional medicinal plants in Southern Africa. A false belief in the safety of herbal medicine may result in liver injury.

Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism.

Many new chemical entities are discovered with high therapeutic potential, however, many of these compounds exhibit unfavorable pharmacokinetic properties due to poor solubility and/or poor membrane permeation characteristics. The latter is mainly due to the lipid-like barrier imposed by epithelial mucosal layers, which have to be crossed by drug molecules in order to exert a therapeutic effect. Another barrier is the pre-systemic metabolic degradation of drug molecules, mainly by cytochrome P450 enzymes located in the intestinal enterocytes and liver hepatocytes.

Beneficial Pharmacokinetic Drug Interactions: A Tool to Improve the Bioavailability of Poorly Permeable Drugs.

Simultaneous oral intake of herbs, supplements, foods and drugs with other drug(s) may result in pharmacokinetic or pharmacodynamic interactions with the latter. Although these interactions are often associated with unwanted effects such as adverse events or inefficacy, they can also produce effects that are potentially beneficial to the patient. Beneficial pharmacokinetic interactions include the improvement of the bioavailability of a drug (i.

Toxicity and anti-prolific properties of Xysmalobium undulatum water extract during short-term exposure to two-dimensional and three-dimensional spheroid cell cultures.

Xysmalobium undulatum (Uzara) is one of the most widely used indigenous traditional herbal remedies in Southern Africa. Commercially available Uzara plant material was used to prepare a crude aqueous extract, of which the toxicity potential was investigated in the hepatic HepG2/C3A cell line in both traditional two-dimensional (2D) and rotating three-dimensional (3D) spheroid cell cultures. These cultures were treated over a period of 4 days at concentrations of 200, 350, 500, and 750 mg/kg plant extract to protein content.

Excipient-drug pharmacokinetic interactions: Effect of disintegrants on efflux across excised pig intestinal tissues.

Pharmaceutical excipients were designed originally to be pharmacologically inert. However, certain excipients were found to have altering effects on drug pharmacodynamics and/or pharmacokinetics. Pharmacokinetic interactions may be caused by modulation of efflux transporter proteins, intercellular tight junctions and/or metabolic enzyme amongst others.

Recent advances in three-dimensional cell culturing to assess liver function and dysfunction: from a drug biotransformation and toxicity perspective.

The liver is a vital organ fulfilling a central role in over 500 major metabolic functions, including serving as the most essential site for drug biotransformation. Dysfunction of the drug biotransformation processes may result in the exposure of the liver (and other organs) to hepatotoxins, potentially interacting with cellular constituents and causing toxicity and various lesions. Hepatotoxicity can be investigated on a tissue, cellular and molecular level by employing various in vivo and in vitro techniques, including novel three-dimensional (3 D) cell culturing methods.

Recent developments in our understanding of the implications of traditional African medicine on drug metabolism.

The use of traditional herbal medicines has become increasingly popular globally, but in some countries, it is the main or sometimes even the only healthcare service available in the most rural areas. This is especially true for Africa where herbal medicines form a key component of traditional medicinal practices and there is access to a diversity of medicinal plants. Although many benefits have been derived from the use of traditional herbal medicines, many concerns are associated with their use of which herb-drug interactions have been identified to have a rising impact on patient treatment outcome.

Topical Delivery of Crude Extracts in Niosomes and Solid Lipid Nanoparticles.

Background: is a medicinal plant native to India and is known to have anticancer properties. It has been investigated for its anti-melanoma properties, and since melanoma presents on the skin, it is prudent to probe the use of in topical formulations. To enhance topical drug delivery and to allow for controlled release, the use of niosomes and solid lipid nanoparticles (SLNs) as delivery vesicles were explored.

In vitro wound healing and cytotoxic activity of the gel and whole-leaf materials from selected aloe species.

Ethnopharmacological Relevance: Aloe vera is one of the most important medicinal plants in the world with applications in the cosmetic industry and also in the tonic or health drink product market. Different parts of Aloe ferox and Aloe marlothii are used as traditional medicines for different applications. Although wound healing has been shown for certain aloe gel materials (e.

Efflux as a mechanism of antimicrobial drug resistance in clinical relevant microorganisms: the role of efflux inhibitors.

Microbial resistance against antibiotics is a serious threat to the effective treatment of infectious diseases. Several mechanisms exist through which microorganisms can develop resistance against antimicrobial drugs, of which the overexpression of genes to produce efflux pumps is a major concern. Several efflux transporters have been identified in microorganisms, which infer resistance against specific antibiotics and even multidrug resistance.

Isolation and in vitro permeation of phenylpropylamino alkaloids from Khat (Catha edulis) across oral and intestinal mucosal tissues.

Ethnopharmacological Relevance: Khat, the leaves of Catha edulis, is used as a "natural amphetamine-like" stimulant in eastern and southern Africa, as well as in the Arabian Peninsula. Leaves are masticated to elicit a state of euphoria. Although the psychostimulatory effects of the leaves are attributed to the presence of phenylpropylamino alkaloids (i.

In vitro oral drug permeation models: the importance of taking physiological and physico-chemical factors into consideration.

The assessment of intestinal membrane permeability properties of new chemical entities is a crucial step in the drug discovery and development process and a variety of in vitro models, methods and techniques are available to estimate the extent of oral drug absorption in humans. However, variations in certain physiological and physico-chemical factors are often not reflected in the results and the complex dynamic interplay between these factors is sometimes oversimplified with in vitro models. Areas covered: In vitro models to evaluate drug pharmacokinetics are briefly outlined, while both physiological and physico-chemical factors that may have an influence on these techniques are critically reviewed.

Combining Chemical Permeation Enhancers for Synergistic Effects.

Currently, macromolecular drugs such as proteins are mainly administered by means of injections due to their low intestinal epithelial permeability and poor stability in the gastrointestinal tract. This study investigated binary combinations of chemical drug absorption enhancers to determine if synergistic drug absorption enhancement effects exist. Aloe vera, Aloe ferox and Aloe marlothii leaf gel materials, as well as with N-trimethyl chitosan chloride (TMC), were combined in different ratios and their effects on the transepithelial electrical resistance (TEER), as well as the transport of FITC-dextran across Caco-2 cell monolayers, were measured.

Skin permeation enhancement effects of the gel and whole-leaf materials of Aloe vera, Aloe marlothii and Aloe ferox.

Objectives: The aim of this study was to investigate the in-vitro permeation enhancement effects of the gel and whole-leaf materials of Aloe vera, Aloe marlothii and Aloe ferox using ketoprofen as a marker compound.

Methods: The permeation studies were conducted across excised female abdominal skin in Franz diffusion cells, and the delivery of ketoprofen into the stratum corneum-epidermis and epidermis-dermis layers of the skin was investigated using a tape-stripping technique.

Key Findings: A.

Review of natural compounds for potential skin cancer treatment.

Most anti-cancer drugs are derived from natural resources such as marine, microbial and botanical sources. Cutaneous malignant melanoma is the most aggressive form of skin cancer, with a high mortality rate. Various treatments for malignant melanoma are available, but due to the development of multi-drug resistance, current or emerging chemotherapies have a relatively low success rates.