Development of Robust Tablet Formulations with Enhanced Drug Dissolution Profiles from Centrifugally-Spun Micro-Fibrous Solid Dispersions of Itraconazole, a BCS Class II Drug.

Fibre-based oral drug delivery systems are an attractive approach to addressing low drug solubility, although clear strategies for incorporating such systems into viable dosage forms have not yet been demonstrated. The present study extends our previous work on drug-loaded sucrose microfibres produced by centrifugal melt spinning to examine systems with high drug loading and investigates their incorporation into realistic tablet formulations. Itraconazole, a model BCS Class II hydrophobic drug, was incorporated into sucrose microfibres at 10, 20, 30, and 50% /.

In vitro and in vivo biological assessment of dual drug-loaded coaxial nanofibers for the treatment of corneal abrasion.

The treatment of corneal abrasion currently involves the topical administration of antibiotics, with moxifloxacin HCl (0.5% w/v) eye drops being one of the most widely used treatments. Our previous work (Tawfik et al.

A Potential Alternative Orodispersible Formulation to Prednisolone Sodium Phosphate Orally Disintegrating Tablets.

The orally disintegrating tablet (ODT) has shown vast potential as an alternative oral dosage form to conventional tablets wherein they can disintegrate rapidly (≤30 s) upon contact with saliva fluid and should have an acceptable mouthfeel as long as their weight doesn't exceed 500 mg. However, owing to the bitterness of several active ingredients, there is a need to find a suitable alternative to ODTs that maintains their features and can be taste-masked more simply and inexpensively. Therefore, electrospun nanofibers and solvent-cast oral dispersible films (ODFs) are used in this study as potential OD formulations for prednisolone sodium phosphate (PSP) that is commercially available as ODTs.

Development and Evaluation of Feline Tailored Amlodipine Besylate Mini-Tablets Using L-lysine as a Candidate Flavouring Agent.

Felines may find orally administered medicines unpalatable, thus presenting a problem in the treatment of chronic conditions such as hypertension, a commonly diagnosed condition in felines requiring daily administration of medication. A pertinent example is amlodipine besylate, formulations of which are known to be poorly tolerated by cats. There is therefore a need to develop feline-specific delivery approaches that are both simple to administer and mask the taste of the drug, thereby enhancing the owner's commitment to treatment and the associated therapeutic outcome for the companion animal.

Dual drug-loaded coaxial nanofibers for the treatment of corneal abrasion.

Corneal abrasion is a scratch wound on the surface of the anterior segment of the eye, which can predispose a patient to corneal infection and scarring, particularly if the cut penetrates to the deep corneal layers. Here we investigate a novel approach to co-administer an anti-scarring agent and an antibiotic, both being incorporated into one dosage form so as to accelerate wound closure and to treat any associated infection. More specifically, we have used electrospun fibers as a means of incorporating the two drugs into distinct compartments via coaxial electrospinning.

Design and Characterization of Cyclosporine A-Loaded Nanofibers for Enhanced Drug Dissolution.

Despite widespread use as an immunosuppressant, the therapeutic efficacy of the undecapeptide cyclosporine A (CyA) is compromised when given by the oral route because of the innate hydrophobicity of the drug molecule, potentially leading to poor aqueous solubility and bioavailability. The aim of this study was to develop and characterize nanofibers based on the water-miscible polymer polyvinylpyrrolidone (PVP), incorporating CyA preloaded into polymeric surfactants so as to promote micelle formation on hydration; therefore, this approach represents the novel combination of three dissolution enhancement methodologies, namely solid dispersion technology, micellar systems, and nanofibers with enhanced surface area. The preparation of the nanofibers was performed in two steps.

In vitro drug release from acetylated high amylose starch-zein films for oral colon-specific drug delivery.

This study describes the preparation of free films of zein with and without acetylated high amylose maize starch (HAS) and their corresponding coated tablets as a novel approach to colonic drug delivery. We hypothesise that the embedding of a digestible starch component within the inert zein would allow the film to remain intact until the large intestine is reached. Free films of zein alone and starch/zein were prepared and characterized.

Investigating the physical stability of repackaged medicines stored into commercially available multicompartment compliance aids (MCAs).

Background: Compliance aids are devices which have been developed and are currently used to assist individuals in their medicines management. The use of compliance aids involves the transfer of medicines from the manufacturers' original packaging and repackaged into an multicompartment compliance aid (MCA). MCAs do not guarantee the same level of protection compared to manufacturer's original packaging.

Microfibrous Solid Dispersions of Poorly Water-Soluble Drugs Produced via Centrifugal Spinning: Unexpected Dissolution Behavior on Recrystallization.

Temperature-controlled, solvent-free centrifugal spinning may be used as a means of rapid production of amorphous solid dispersions in the form of drug-loaded sucrose microfibers. However, due to the high content of amorphous sucrose in the formulations, such microfibers may be highly hygroscopic and unstable on storage. In this study, we explore both the effects of water uptake of the microfibers and the consequences of deliberate recrystallization for the associated dissolution profiles.

Plant-expressed Hepatitis B core antigen virus-like particles: Characterization and investigation of their stability in simulated and pig gastro-intestinal fluids.

Virus-like particles (VLPs) are potential oral vaccine candidates, as their highly compact structure may allow them to withstand the harsh conditions of the gastro-intestinal (GI) environment. Hepatitis B core antigen (HBcAg) is an immunogenic protein that assembles into 30 or 34nm diameter VLPs. Here, the stabilities of both the HBcAg polypeptide itself and the three-dimensional structure of the VLPs upon exposure to in vitro and ex vivo simulated gastric and intestinal fluids were investigated.

Development of micro-fibrous solid dispersions of poorly water-soluble drugs in sucrose using temperature-controlled centrifugal spinning.

Solid dispersion technology represents a successful approach to addressing the bioavailability issues caused by the low aqueous solubility of many Biopharmaceutics Classification System (BCS) Class II drugs. In this study, the use of high-yield manufacture of fiber-based dispersion is explored as an alternative approach to monolith production methods. A temperature-controlled solvent-free centrifugal spinning process was used to produce sucrose-based microfibers containing the poorly water-soluble drugs olanzapine and piroxicam (both BCS Class II); these were successfully incorporated into the microfibers and the basic characteristics of fiber diameter, glassy behavior, drug loading capacity and drug-sucrose interaction assessment were measured.

Development of photothermal FTIR microspectroscopy as a novel means of spatially identifying amorphous and crystalline salbutamol sulfate on composite surfaces.

Photothermal Fourier transform infrared (FTIR) microspectroscopy (PTMS), involving the combination of FTIR spectroscopy with atomic force microscopy, has been used to examine compacts of amorphous and crystalline salbutamol sulfate in order to assess the ability of the technique to distinguish between different physical forms in a multicomponent material. Samples of amorphous and crystalline material were assessed using modulated temperature differential scanning calorimetry (DSC), atomic force microscopy, microthermal analysis, and conventional FTIR. Mixed compacts were then prepared such that verification of the location of the forms present was possible via topography and localized thermal analysis.

Development of fully amorphous dispersions of a low T(g) drug via co-spray drying with hydrophilic polymers.

The aim of the study was to prepare molecular dispersions of a physically highly unstable amorphous drug, paracetamol (acetaminophen with a T(g) of ca. 25°C) via co-spray drying with a variety of polymers. Solid dispersions at a range of drug loadings (10-90%w/w) using hydroxypropyl methylcellulose/acetate succinate (HPMC/HPMC AS), polyvinylpyrrolidone (PVP) and copovidone were produced and characterised by modulated temperature differential scanning calorimetry (MTDSC), thermogravimetric analysis (TGA), X-ray powder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM).

An investigation into water interactions with amorphous and milled salbutamol sulphate: the development of predictive models for uptake and recrystallization.

An investigation into the effect of water uptake on the glass transition of spray dried and milled salbutamol sulphate has been performed, with a particular view to exploring how the water uptake, T(g) value and recrystallization behaviour correlate. Samples of milled and spray dried drug were stored under controlled humidity conditions and the T(g) measured as a function of time. The T(g) was measured using modulated temperature differential scanning calorimetry (MTDSC) while the water content was measured using thermogravimetric analysis (TGA).

Characterization and quantification of amorphous material in milled and spray-dried salbutamol sulfate: a comparison of thermal, spectroscopic, and water vapor sorption approaches.

A study has been undertaken using a range of established and novel approaches to examine the effects of milling on the structure and crystallization behavior of salbutamol sulfate. A combination of modulated temperature differential scanning calorimetry, attenuated total reflectance Fourier-transform infrared spectroscopy, powder X-ray diffraction, and gravimetric vapor sorption analysis have been employed, with a particular view to examining the validity of using spray-dried material as a comparator. Although the expected increase in amorphization with milling time was observed, several unexpected observations were made including an apparently anomalous relationship between glass transition temperature and water content; this was used as the basis for the development of a novel method of quantifying amorphous content.

The effect of composition and gastric conditions on the self-emulsification process of ibuprofen-loaded self-emulsifying drug delivery systems: a microscopic and dynamic gastric model study.

Purpose: To investigate the physical processes involved in the emulsification of self-emulsifying drug delivery systems (SEDDSs) and the use of the Dynamic Gastric Model (DGM) as a characterisation tool.

Methods: SEDDSs based on soybean oil, Tween 80, Span 80 and ibuprofen were prepared and their equilibrium phase diagrams established. The emulsification behaviour in a range of media was studied using polarised light microscopy and particle sizing.

Zein-iodine complex studied by FTIR spectroscopy and dielectric and dynamic rheometry in films and precipitates.

In the present study the effect of iodine on properties of zein films and zein precipitates obtained after hydrophobic aggregation was evaluated. Zein films were cast with and without glycerol (as plasticizer) after incorporation of iodine at different levels (2-8%, zein wt basis). Zein films were characterized by secondary structure (determined by infrared spectroscopy) and dielectric and mechanical properties.

Plasticization of zein: a thermomechanical, FTIR, and dielectric study.

Zein, the main seed storage protein of maize, has been widely studied as a possible source of material for the production of biodegradable plastic films. Plasticization of zein is critical to make functional films. While there have been a number of publications which report the behavior of systems with a wide variety of plasticizers, there have been few which attempt to examine the interactions of protein and plasticizer at the molecular level.

Oral bioavailability enhancement of a hydrophilic drug delivered via folic acid-coupled liposomes in rats.

Objectives: A liposome preparation that is amenable to receptor-mediated endocytosis has been developed to enhance the oral bioavailability of poorly absorbable peptidomimetic drugs by use of folic acid as the mediator of liposomal uptake.

Methods: Folic acid was physically coupled to the surface of the liposomes and cefotaxime was used as the model drug. In-vivo evaluation was carried out on eight Sprague-Dawley rats in a two-way crossover study to compare the oral bioavailability of cefotaxime loaded in folic acid-free liposomes and folic acid-coupled liposomes.

A study on maize proteins as a potential new tablet excipient.

This investigation has examined the use of zein proteins from maize as the major component in oral controlled-release tablets, such formulations often being required to improve patient compliance. Tablets containing ground zein proteins, calcium hydrogen orthophosphate, polyvinyl pyrrolidone, theophylline and magnesium stearate were produced by wet granulation and compression on a single station tablet press and were compared to directly compressed tablets based on zein proteins, calcium hydrogen orthophosphate and theophylline. Non invasive techniques such as Fourier Transform infrared spectroscopy and Fourier Transform Raman spectroscopy were employed to investigate any changes in the secondary structure of zein proteins during tablet production.

The role of space charge formation in the generation of thermally stimulated current (TSC) spectroscopy data for a model amorphous drug system.

Thermally stimulated current (TSC) spectroscopy is attracting increasing attention as a means of materials characterization, particularly in terms of measuring slow relaxation processes in solid samples. However, wider use of the technique within the pharmaceutical field has been inhibited by difficulties associated with the interpretation of TSC data, particularly in terms of deconvoluting dipolar relaxation processes from charge distribution phenomena. Here, we present evidence that space charge and electrode contact effects may play a significant role in the generation of peaks that have thus far proved difficult to interpret.

A laser imaging and neutron reflection investigation into the monolayer behaviour of fatty acids used for taste masking microspheres.

Fatty acid microspheres have been used for taste masking purposes whereby the drug is preferentially released in the lower gastrointestinal tract, although the mechanisms involved are poorly understood. In this study, we use a combination of surface pressure measurements, Brewster angle microscopy (BAM) and neutron reflectivity measurements to study the phase miscibility and escaping tendency from mixed stearic and palmitic acid films with a view to relating this to drug dissolution behaviour. It was noted that mixed systems showed considerably greater film interaction and instability than those composed of the pure lipid, especially in alkaline media.

Hydration of gluten: a dielectric, calorimetric, and fourier transform infrared study.

The nature of the hydration of proteins and the subsequent implications for functionality is a matter of importance in both pharmaceutical and food applications. Most published studies rely on the use of one technique and attempt to characterize the system. Few studies have used combinations of techniques.

Enhanced oral bioavailability and intestinal lymphatic transport of a hydrophilic drug using liposomes.

A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes.