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% /.

Multi-Analytical Framework to Assess the In Vitro Swallowability of Solid Oral Dosage Forms Targeting Patient Acceptability and Adherence.

A lack of effective intervention in addressing patient non-adherence and the acceptability of solid oral dosage forms combined with the clinical consequences of swallowing problems in an ageing world population highlight the need for developing methods to study the swallowability of tablets. Due to the absence of suitable techniques, this study developed various in vitro analytical tools to assess physical properties governing the swallowing process of tablets by mimicking static and dynamic stages of time-independent oral transitioning events. Non-anatomical models with oral mucosa-mimicking surfaces were developed to assess the swallowability of tablets; an SLA 3D printed in vitro oral apparatus derived the coefficient of sliding friction and a friction sledge for a modified tensometer measured the shear adhesion profile.

Patient-Centric Medicine Design: Key Characteristics of Oral Solid Dosage Forms that Improve Adherence and Acceptance in Older People.

Older people represent a very heterogeneous patient population and are the major user group of medication. Age-related changes mean that this population can encounter barriers towards taking medicines orally. The aim of this study was to investigate the characteristics of oral solid dosage forms that contribute to an age appropriate dosage design, with an aim to improve overall medication adherence and acceptance in older people.

Investigation of water vapour sorption mechanism of starch-based pharmaceutical excipients.

Starch-based excipients are commonly used in oral solid dosage forms. The effect of particle size and pregelatinisation level of starch-based excipients on their water absorption behaviour have been evaluated. The results showed that starch-based excipients have type ii isotherms, indicating that the principal mechanism of sorption is the formation of monolayer coverage and multilayer water molecules (10-80 RH %).

Does the Formulation of Oral Solid Dosage Forms Affect Acceptance and Adherence in Older Patients? A Mixed Methods Systematic Review.

Objectives: Age-related changes mean that the older population can encounter barriers toward taking medication orally. Further work is needed to identify the characteristics of oral solid dosage forms that will improve patient acceptance and adherence. The aim of this systematic review was to identify if and how formulation aspects of oral solid dosage forms affect acceptance and adherence in older people.

Conceptualisation, Development, Fabrication and In Vivo Validation of a Novel Disintegration Tester for Orally Disintegrating Tablets.

Disintegration time is the key critical quality attribute for a tablet classed as an Orally Disintegrating Tablet (ODT). The currently accepted in vitro testing regimen for ODTs is the standard United States Pharmacopeia (USP) test for disintegration of immediate release tablets, which requires a large volume along with repeated submergence of the dosage form within the disintegration medium. The aim of this study was to develop an in vivo relevant ODT disintegration test that mimicked the environment of the oral cavity, including lower volume of disintegration medium, with relevant temperature and humidity that represent the conditions of the mouth.

Robustness of barrier membrane coated metoprolol tartrate matrix tablets: Drug release evaluation under physiologically relevant in vitro conditions.

Robust in vitro drug release behavior is an important feature of extended release (ER) hydrophilic matrix formulations for accurate prediction of in vivo drug release. In this study, ER hydrophilic matrix tablets of metoprolol tartrate were formulated using a high viscosity grade of hypromellose as a rate-limiting polymer. Expectedly, this formulation showed an undesirable initial burst release followed by controlled drug release.

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.

The Properties of HPMC:PEO Extended Release Hydrophilic Matrices and their Response to Ionic Environments.

Purpose: Investigate the extended release behaviour of compacts containing mixtures of hydrophilic HPMC and PEO in hydrating media of differing ionic strengths.

Methods: The extended release behaviour of various HPMC:PEO compacts was investigated using dissolution testing, confocal microscopy and magnetic resonance imaging, with respect to polymer ratio and ionic strength of the hydrating media.

Results: Increasing HPMC content gave longer extended release times, but a greater sensitivity to high ionic dissolution environments.

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.

Application of ethylcellulose coating to hydrophilic matrices: a strategy to modulate drug release profile and reduce drug release variability.

Hydrophilic matrix tablets are commonly used for extended release dosage forms. For low aqueous-solubility drugs, there may be challenges in modulation of release profiles and achieving consistent release in physiological conditions. To evaluate potential formulation strategies, matrix tablets of a low-soluble drug, hydrochlorothiazide, were developed using hypromellose and two fillers of different solubility, lactose (soluble) or partially pregelatinized maize starch (partially soluble).

Investigation of critical core formulation and process parameters for osmotic pump oral drug delivery.

Push-pull osmotic pump (PPOP) tablets of a practically insoluble model drug were developed and the effect of various formulation and process parameters on tablet performance was evaluated in order to identify critical factors. The formulation factors such as the viscosity grade of polyethylene oxide as the primary polymer as well as the level and location of osmogen within the bilayer tablets led to a difference in performance of osmotic tablets and hence should be critically evaluated in the design of such dosage forms. Modification of granulation process, i.

Delayed release film coating applications on oral solid dosage forms of proton pump inhibitors: case studies.

Background: Formulation of proton pump inhibitors (PPIs) into oral solid dosage forms is challenging because the drug molecules are acid-labile. The aim of this study is to evaluate different formulation strategies (monolithic and multiparticulates) for three PPI drugs, that is, rabeprazole sodium, lansoprazole, and esomeprazole magnesium, using delayed release film coating applications.

Method: The core tablets of rabeprazole sodium were prepared using organic wet granulation method.

Investigation of the effects of hydroalcoholic solutions on textural and rheological properties of various controlled release grades of hypromellose.

Hypromellose (hydroxypropyl methylcellulose, HPMC) matrices are widely used in the formulation of sustained release dosage forms. The integrity and performance of an HPMC matrix formulation depends on rapid hydration and gel formation upon ingestion. Due to the recent alert issued by the Food and Drug Administration regarding the potential negative influence of alcoholic beverages on extended release (ER) formulations, several researchers have evaluated the potential influence of hydroalcoholic media on drug release from ER dosage forms.

Application of powder rheometer to determine powder flow properties and lubrication efficiency of pharmaceutical particulate systems.

The objective of this study was to understand the behavior of particulate systems under different conditions of shear dynamics before and after granulation and to investigate the efficiency of powder lubrication. Three drug powders, metronidazole, colloidal bismuth citrate, and tetracycline hydrochloride, were chosen as model drugs representing noncohesive and cohesive powder systems. Each powder was individually granulated with microcrystalline cellulose and 5%PVP as a binder.

Release characterization of dimenhydrinate from an eroding and swelling matrix: selection of appropriate dissolution apparatus.

The objective of this study was to evaluate the effect of various hydrodynamic conditions on drug release from an eroding and gel forming matrix. For this purpose, dimenhydrinate was formulated with hydroxypropyl methyl cellulose and polyethylene oxide into matrix tablets and the drug release in deionized water was evaluated spectrophotometrically, using multiple dissolution methods, namely, compendial USP 27-apparatus I-III, and a modified apparatus II (paddle over mesh). Various hydrodynamic conditions were examined at the agitation rates of 50 and 100 rpm for apparatus I and II, and 5 and 8 dpm for apparatus III.

A novel approach in the assessment of polymeric film formation and film adhesion on different pharmaceutical solid substrates.

The purpose of this study was to evaluate the nature of film formation on tablets with different compositions, using confocal laser scanning microscopy (CLSM), and to measure film adhesion via the application of a novel "magnet probe test." Three excipients, microcrystalline cellulose (MCC), spray-dried lactose monohydrate, and dibasic calcium phosphate dihydrate, were individually blended with 0.5% magnesium stearate, as a lubricant, and 2.