The role of force control agents in high-dose dry powder inhaler formulations.

The aim of this study was to determine the aerosolisation and aerodynamic properties of model inhalation particles (salbutamol sulphate and budesonide) upon coprocessing with force control agents (FCAs)-leucine, lecithin and magnesium stearate. Coprocessing of the drug particles with FCAs (5%, w/w) was conducted using mechanofusion-a novel dry mechanical fusion process. The influence of mechanofused FCAs on the entrainment and deaggregation behaviour of the drug-only formulations was investigated using a next generation impactor (NGI) and an in-line Spraytec laser diffraction particle sizer.

Surface energy of microcrystalline cellulose determined by capillary intrusion and inverse gas chromatography.

Surface energy data for samples of microcrystalline cellulose have been obtained using two techniques: capillary intrusion and inverse gas chromatography. Ten microcrystalline cellulose materials, studied using capillary intrusion, showed significant differences in the measured surface energetics (in terms of total surface energy and the acid-base characteristics of the cellulose surface), with variations noted between the seven different manufacturers who produced the microcrystalline cellulose samples. The surface energy data from capillary intrusion was similar to data obtained using inverse gas chromatography with the column maintained at 44% relative humidity for the three samples of microcrystalline cellulose studied.

Effect of moisture on the compressibility and compactibility of sodium starch glycolate.

The relationship between the apparent moisture content and compactibility of sodium starch glycolate was compared to similarly obtained data for pregelatinized starch. Samples of sodium starch glycolate (SSG) and pregelatinised starch (PGS) were stored at 44% or 75% relative humidity (RH), producing samples exhibiting moisture contents of up to 14% w/w, as determined by loss on drying (LOD). Increasing the moisture content of SSG and PGS resulted in an increase in compressibility and compactibility for both materials.

Interaction of moisture with sodium starch glycolate.

The relationship between the apparent moisture content and moisture sorption of modified starches was investigated. Samples of sodium starch glycolate (SSG), pregelatinized starch (PGS) and potato starch (PS) were stored for various times at 44% or 75% relative humidity (RH) to produce samples with moisture contents of up to 14%, as determined by loss on drying (LOD). Evaluation of LOD and mass gain data suggested that measured mass gain equated to predicted LOD values for PGS and PS.

Interactions of water with the surfaces of crystal polymorphs.

The purpose of this study is to investigate the interactions of water adsorption on the surfaces of different crystal forms of the same drug. The energy of interaction between water vapor and the surfaces of the two crystal polymorphs has been investigated as a function of temperature and water activity. One of the adsorbents, the metastable form of the monotropically related pair used here, showed greater adsorptive capacity in terms of both the amount of water uptake as well the integral heat of adsorption.

TIMERx: novel polysaccharide composites for controlled/programmed release of drugs in the gastrointestinal tract.

Over the last 100 years tablets have grown from first invention to becoming the world's leading medicinal form, by any measure. This article considers some of the reasons for the pre-eminence of pharmaceutical tablets. Particular attention has been given to the role of controlled-release tablets and to a very versatile hydrogel-based controlled-release technology, called TIMERx((R)).

Dynamic vapor sorption properties of sodium starch glycolate disintegrants.

Dynamic vapor sorption (DVS) was used to determine the moisture sorption properties of sodium starch glycolates. The results were compared to similarly obtained data for potato starch, pregelatinized starch, microcrystalline cellulose (MCC), and crystalline lactose. As expected, sodium starch glycolates exhibit a large mass gain at 90% relative humidity (RH), compared to the other anhydroglucose-based excipients.

The cohesive-adhesive balances in dry powder inhaler formulations II: influence on fine particle delivery characteristics.

Purpose: To investigate the influence of the cohesive-adhesive balances on dry powder formulation aerosolization and delivery characteristics.

Methods: De-agglomeration properties of pharmaceutical powders were investigated using an Aerosizer at various shear forces. Aerosol drug deposition properties of drug-only formulations and carrier-based formulations were investigated using a low-resistance device (Rotahaler) and a high-resistance device (Turbuhaler) via a twin-stage impinger.

The cohesive-adhesive balances in dry powder inhaler formulations I: Direct quantification by atomic force microscopy.

Purpose: To obtain a quantitative assessment of the cohesive and adhesive force balance within dry powder inhaler formulations.

Methods: The atomic force microscope (AFM) colloid probe technique was used to measure the adhesive and cohesive force characteristics of dry powder systems containing an active component (budesonide, salbutamol sulphate) and alpha-lactose monohydrate. To minimize the variations in contact area between colloid probe and substrates, nanometer smooth crystal surfaces of the drugs and the excipient were prepared.

Active and intelligent inhaler device development.

The dry powder inhaler, which has traditionally relied on the patient's inspiratory force to deaggregate and deliver the active agent to the target region of the lung, has been a successful delivery device for the provision of locally active agents for the treatment of conditions such as asthma and chronic obstructive pulmonary disease (COPD). However, such devices can suffer from poor delivery characteristics and/or poor reproducibility. More recently, drugs for systemic delivery and more high value compounds have been put into DPI devices.

Physicochemical and mechanical evaluation of a novel high density grade of silicified microcrystalline cellulose.

High density microcrystalline cellulose (MCC) is a relatively free flowing grade of MCC that finds use in direct compression tableting and hard gelatin capsule filling applications. Silicified high density microcrystalline cellulose has recently been introduced. This material has been compared to other grades of MCC and previously silicified microcrystalline cellulose (SMCC).

Development and evaluation of bio-dissolution systems capable of detecting the food effect on a polysaccharide-based matrix system.

Methods are proposed and tested for mimicking the in vitro food effect on controlled release dosage forms, using USP dissolution apparatus 3. Using in vivo data a pH and time profile was constructed, and the methods utilized either presoaking in peanut oil or continuous oil contact to mimic the presence of a high fat meal. A water soluble drug (propranolol hydrochloride, class 1 by BCS) was used as a model material.

Adsorption of an amine drug onto microcrystalline cellulose and silicified microcrystalline cellulose samples.

The adsorption of a model amine drug (tacrine hydrochloride) from aqueous solution onto 21 microcrystalline cellulose (MCC) based samples has been investigated. The MCC source (manufacturer) affected adsorption. The adsorption appeared to be fully reversible.