Solid/Semi-Solid Dosage

Bin blender performance is comprehensively reviewed using both free-flowing and cohesive mixtures.

Dry powder inhalers are a well-accepted dosage form for pulmonary drug delivery and a wide variety are either currently available or in development. This article examines a premetered, capsule-based multidose inhaler for which different qualities of a-lactose monohydrate were screened.

The bioavailability of some insoluble drugs is enhanced when they are dissolved in the solubilizing agent macrogol 400, although conventional hard capsules cannot tolerate the agent. This article investigates a PVA copolymer, which has been developed by the authors, examining its properties and its suitability as a material in capsule formulations.

This article describes the use of a one-pot processor for the cleaning and cleaning validation of two drug compounds - water-soluble theophylline and water-insoluble mebendazole. Both substances were produced using wet granulation and microwave drying, after which the processor was cleaned using its clean-in-place (CIP) system. Swab samples were taken from areas considered critical during processing and analysed for remains of active ingredient. It was concluded from the results that the processor's CIP system is capable of removing both moieties to a level well within accepted regulations.

The authors examine the development and performance of coprocessed excipients, including testing them for flowability, compressibility, amd dilution potential.

This article reflects on the challenges that predicting powder flowability currently pose to the pharmaceutical manufacturing industry and considers some of the benefits that can accrue when companies overcome these issues.

The use of solid dispersion technology to increase the bioavailability of poorly water-soluble drugs has always been limited by processing and scale-up difficulties. A new approach may help to overcome some of the problems.

The aim of this study was to validate the automated clean-in-place (CIP) system installed on a capsule filling machine to determine its ability to adequately eliminate contaminants. The results obtained from the proposed cleaning validation trial showed that all the soluble tracer was removed after the washing procedure. At the end of the CIP procedure, the discharged water had the same pH, phosphate content and total organic content as the supplied water. Lack of cross-contamination in the product was also demonstrated and a recovery trial highlighted the complete elimination of the tracer from the machine.

This article describes a method for assessing the similarity of dissolution profiles using Hotelling's T2 statistic. The method applies a covariance structure that accounts for the heterogeneity of variance and correlation across time points. Comparing the method with the f2 criterion recommended in FDA's guidance on dissolution testing, the performance of the two methods was assessed on real examples, and simulation studies were also done to compare the method's performance with that of the f2 criterion.

Modern tablet production facilities are faced with two increasingly important, yet contradictory, demands - being able to handle more potent drugs and, at the same time, reduce costs. Additionally, batch sizes must become smaller and production planning more flexible. Until recently, these issues could only be dealt with individually and not as a whole; however, the exchangeable functional module (EFM) may provide a solution to this problem, as this article describes.

The authors provide a combined source of density data and show that denity can be used as an equipment-independent sclaing parameter in the manufacture of common pharmaceutical solids.

Oral dosage forms are the most popular way of taking medication, despite having some disadvantages compared with other methods. One such disadvantage is the risk of slow absorption of the active pharmaceutical ingredient (API), which can be overcome by administering the drug in liquid form and, therefore, possibly allowing the use of a lower dosage.

Binder properties of mucilage of starches extracted from breadfruit and cocoyam were investigated in paracetamol tablet formulations using tablet physical properties, disintegration times, and dissolution rates as assessment parameters.

The tabletting properties of a new coprocessed excipient for direct compression were compared with a physical mixture of its components (separately and with drugs) and the individual constituents. The compaction properties were also investigated. Results indicated that the new excipient has excellent flow properties and demonstrates enhanced compressibility.

Medicines and excipients are inseparable, with few exceptions - one cannot exist without the other. The Pharmaceutical Quality Group and other international bodies have developed good manufacturing practice (GMP) standards and guidelines to facilitate the effective supply of excipients. This article discusses the definition and significance of excipients, and highlights the importance of implementing the correct excipient manufacturing controls and standards.

Consideration of the key process variable will define the ease with which coating processes can be transferred from development to production. This study investigates those factors influencing atomization from two spray guns and examines how development-scale procedures on interchangeable drum coating equipment compare with those typically used in a production environment.

The aim of this work was to investigate the compactibility, compressibility and drug release behaviour of different fractions of a commercially available ethyl cellulose.

Dry powder inhalers (DPIs) contain a powder which, when required, is discharged and inhaled. The therapeutic drug is manufactured in powder form as small particles a few micrometres in diameter. In many DPIs, the drug is mixed with much larger sugar crystals, such as lactose, and the smaller drug particles attach to these excipient particles, improving entrainment of the drug upon inhalation. This article examines how the application and combination of versatile processes such as milling, micronizing, sieving and air classification can be used to manufacture dedicated lactose products for practically every possible combination of active and excipient blend in DPIs.

The author offers a primer for choosing the correct granulation process to improve yields, reduce tablet defects, and enhance productivity.

Using melt extrusion to prepare glass solutions of poorly water-soluble drugs with hydrophilic excipients offers an exciting and advantageous alternative to existing formulation methods such as spray-drying and co-melting. Investigating potential methods to increase water solubility begins early in drug development. Techniques described in this paper show how only a small quantity of drug can be used to determine its suitability for melt extrusion, allowing the method to be considered at the same time as salt screening and particle size reduction work, and could speed up the formulation process.

High quality tablet compression tooling is expensive, albeit consumable. With the potential for tooling damage during tablet production, transportation and storage, an acceptable method of cleaning, repairing, validating and storing tooling is required by anyone who manufactures tablets - and the regulatory inspection authorities.

Decision-making tools such as expert systems and artificial neural networks can be integrated to facilitate the development of optimal formulations of hard gelatin capsules.

Spreadability of a semisolid forrmulation is affected by factors such as formulation characteristics, rate and time of shear, temperature, site of application, and the presence of various additives.

Dynamic powder-sampling methods may be the best techniques for obtaining a representative sample for determining particle-size distribution.

Powdered self-emulsified dosage forms provide an attractive alternative to filled-capsule preparations, but the selection of a proper excipient is crucial.

Semisolid dosage forms are advantageous in terms of their easy application, rapid formulation, and ability to topically deliver a wide variety of drug molecules.

The delivery agent-mediated transport of low moleular weight heparin across Caco-2 cells is accomplished without opening the junctions or adversely affecting the structural integrity of the cell monolayer.

Low levels of some microorganisms that are present in oral solid dosage forms are unlikely to present a risk to patients. The amount of water activity in these products can help determine when microbiological testing should be conducted.

To achieve the maximum performance from a tablet press run, operators must learn to distinguish between machine-related issues and granulation-related issues.

Tablet manufacturers often overlook critical basic concepts or established practices. The author draws from his own experiences and discusses how solid dosage manufacturers can improve production and product quality by optimizing major unit operations.