Zhi Hui Loh

Spray granulation for drug formulation

Introduction: Granulation is a key unit process in the production of pharmaceutical solid dosage forms and involves the agglomeration of fine particles with the aid of a binding agent. Fluidized bed granulation, a classic example of spray granulation, is a technique of particle agglomeration brought about by the spray addition of the binding liquid onto a stationary bed of powder particles that is transformed to a fluid-like state by the passage of air through it. Areas covered: The basic working principles, equipment set-up, advantages and challenges of fluidized bed granulation are introduced in this review. This is followed by an overview of the formulation and process-related variables affecting granulation performance. Technological advances, particularly in the application of process analytical tools, in the field of fluidized bed granulation research are also discussed. Expert opinion: Fluidized bed granulation is a popular technique for pharmaceutical production, as it is a highly economical and efficient one-pot process. The research and development of process analytical technologies (PAT) has allowed greater process understanding and control to be achieved, even for the lesser known fluidized bed techniques, such as bottom spray and fluidized hot melt granulation. In view of its consistent mixing, as well as continuous and concurrent wetting and drying occurring throughout processing, fluidized bed granulation shows great potential for continuous production although more research is required to fully implement, validate and integrate the PAT tools in a production line.

Microwave-assisted drying of pharmaceutical granules and its impact on drug stability

The advent of microwave technology has intensified the search for pharmaceuticals amenable to microwave processing. This study investigated the influences of powder load, diluent particle size and amount of granulating liquid employed on the microwave-assisted drying and stability of acetylsalicylic acid (ASA)-loaded granules in a single pot high shear processor. Powder load affected the profiles, rate and extent of drying. Drying was more dependent on the size and structural properties of granules rather than their surface areas as heat was generated volumetrically. Increased granule size brought about by increasing the size of diluent particles and amount of granulating liquid resulted in higher drying rates. Drug stability was negatively correlated to the drying time of granules.

Distribution of a viscous binder during high shear granulation—Sensitivity to the method of delivery and its impact on product properties

Binder distribution in the powder mass during high shear granulation is especially critical with the use of viscous liquid binders and with short processing times. A viscous liquid binder was delivered into the powder mass at two flow rates using three methods: pouring, pumping and spraying from a pressure pot. Binder content analyses at the scale of individual granules were conducted to investigate the impact of different delivery conditions on the homogeneity of binder distribution. There was clear evidence of non-uniformity of binder content among individual granules across all delivery conditions, particularly for the fast rates of delivery. Poorer reproducibility values of tablet thickness and disintegration time were observed when binder was poured but this may be overcome by pumping or spraying from the pressure pot. Greater homogeneity of binder distribution occurred with the slow rates of delivery and led to the earlier onset of granule growth and a consequent increase in granule size. Larger granule size and lower proportion of fines were in turn associated with increased granule bulk density and improvement of granule flow. In conclusion, delivery of a viscous binder at a slow rate either by pumping or via a pressure pot was most desirable during granulation.

A Study on Microwave-Induced Melt Granulation in a Single Pot High Shear Processor

Microwave-induced high shear melt granulation was compared with conventional melt granulation performed in the same processor. Admixtures of lactose 200M and anhydrous dicalcium phosphate were granulated with polyethylene glycol 3350. Different heating mechanisms in the two processes necessitated the use of different parameters for process monitoring and control. Mixer power consumption was suitable for monitoring agglomerate growth under microwave-induced heating. Product temperature was a better indicator of agglomeration propensity in conventional melt granulation. These were attributed to the disparities in heat acquisition rates and heating uniformities of the powders as well as variation in baseline mixer power consumption between the two processes.

Stability of a novel corticosteroid nasal irrigation solution: betamethasone 17‐valerate added to extemporaneously prepared nasal irrigation solutions

There are no commercially available nasal irrigation solutions containing corticosteroids. Instead, such preparations are extemporaneously prepared by adding existing corticosteroid formulations to nasal irrigation solutions. The stability of the corticosteroid betamethasone 17‐valerate (B17V), in nasal irrigation solutions of different compositions and pH and stored under different temperatures, was studied to determine the optimal choice of solution and storage conditions.

Effect of moisture sorption on the performance of crospovidone

Crospovidone is a commonly used tablet disintegrant. However, the synthetic disintegrant has been known to be hygroscopic and high moisture content in crospovidone used could exert deleterious effects on tablets formulated with it. The objective of this study was to elicit a better understanding between crospovidone-water interaction and its effect on disintegrant performance. Moisture sorption and desorption isotherms were obtained together with the enthalpy of immersion. Crospovidone samples stored at four relative humidities were used to formulate tablets and the resultant tablets were evaluated for their mechanical, dimensional and disintegratability attributes. Analyses of the moisture sorption isotherms indicated that externally adsorbed moisture accounted for the bulk of the total moisture content in crospovidone, with minimal amount of moisture absorbed intramolecularly. Enthalpy of immersion became less exothermic with crospovidone samples stored at increasing storage humidity. Correspondingly, improvement in disintegration time became less pronounced. This was postulated to be a consequence of premature wetting of the particle surfaces by externally adsorbed moisture. High humidity was also detrimental to tablet hardness and thickness. In conclusion, the impact of moisture sorption during storage by excipients such as crospovidone could be better understood by the appreciation of crospovidone-water interaction and its consequence on tablet quality.