Influence of Batch Cooling Crystallization on Mannitol Physical Properties and Drug Dispersion from Dry Powder Inhalers

Kaialy, Waseem; Larhrib, Hassan; Ticehurst, Martyn D.; Nokhodchi, Ali

doi:10.1021/cg300224w

Cited by 28 publications

(22 citation statements)

References 35 publications

(82 reference statements)

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“…Optical image analysis microscopy was employed to quantify shape of the HPMC E4M and K4M particles using several shape descriptors including roundness [21] and roughness [22].…”

Section: Particle Shape Analysismentioning

confidence: 99%

The influence of agitation sequence and ionic strength on in vitro drug release from hypromellose (E4M and K4M) ER matrices—The use of the USP III apparatus

Asare-Addo

Kaialy

Levina³

et al. 2013

Colloids and Surfaces B: Biointerfaces

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Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC) E4M and K4M were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The objectives of this study were to evaluate the effects of systematic agitation, ionic strength and pH on the release of theophylline from the gel forming hydrophilic polymeric matrices with different methoxyl substitution levels. Tribo-electric charging of hypromellose, theophylline and their formulated blends containing E4M and K4M grades has been characterised, along with quantitative observations of flow, compression behaviour and particle morphology.Agitations were studied at 5, 10, 15, 20, 25, 30 dips per minute (dpm) and also in the ascending and descending order in the dissolution vials. The ionic concentration strength of the media was also varied over a range of 0-0.4 M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. To study the effect of ionic strength on the hydrophilic matrices, agitation was set at 20 dpm. The charge results on individual components imply that the positively charged particles have coupled with the negatively charged particles to form a stable ordered mixture which is believed to result in a more homogeneous and stable system. The particle shape analysis showed the HPMC K4M polymer to have a more irregular morphology and a rougher surface texture in comparison to the HPMC E4M polymer, possibly a contributory factor to the gelation process. The results showed gelation occurred quicker for the K4M tablet matrices. Drug release increased with increased agitation. This was more pronounced for the E4M tablet matrices. The ionic strength also had more of an effect on the drug release from the E4M matrices. The experiments highlighted the resilience of the K4M matrices in comparison with the E4M matrices. The results thus show that despite similar viscosities of E4M and K4M, the methoxyl substitution makes a difference to their control of drug release and as such care and 3 consideration should be given to the choice of polymer used for extended release. The use of systematic change of agitation method and ionic strength may indicate potential fed and fasted effects on drug release from hydrophilic matrices.

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“…Optical image analysis microscopy was employed to quantify shape of the HPMC E4M and K4M particles using several shape descriptors including roundness [21] and roughness [22].…”

Section: Particle Shape Analysismentioning

confidence: 99%

The influence of agitation sequence and ionic strength on in vitro drug release from hypromellose (E4M and K4M) ER matrices—The use of the USP III apparatus

Asare-Addo

Kaialy

Levina³

et al. 2013

Colloids and Surfaces B: Biointerfaces

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“…To provide further evidence to support this mechanism, SS-lactose adhesion characteristics were (indirectly) evaluated by submitting the adhesive mixtures blended for different times to air-depression sieving [82][83][84]. This allows the carrier particles to be examined for the carrier residue (CR, % drug remaining on carrier surfaces after sieving) after different sieving times.…”

Section: Blending Time and Speedmentioning

confidence: 99%

On the effects of blending, physicochemical properties, and their interactions on the performance of carrier-based dry powders for inhalation — A review

Kaialy

2016

Advances in Colloid and Interface Science

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Blending drug and carrier powders to produce homogeneous drug-carrier adhesive mixtures is a key step in the production of dry powder inhaler (DPI) formulations. Although the blending conditions can result in different conclusions or probably change the outcome of a study entirely if being selected differently, there is a scarcity of data on the influence of blending processes on the physicochemical properties of bulk powder formulations and the follow-on effects on DPI performance. This paper provides an overview of the interactions between variables related to blending conditions (e.g. blending equipment, time, speed and sequence as well as environmental humidity) and powder physicochemical properties (e.g. size distribution, shape distribution, density, anomeric composition, electrostatic charge, surface, and bulk properties), and their effects on the performance of adhesive mixtures for inhalation in terms of drug content homogeneity, drug-carrier adhesion, and drug aerosolisation behaviour. The relevance of carrier payload, batch size and segregation was also discussed. Challenges and future directions were identified. This review therefore contributes towards a better understanding of the blending process, powder physicochemical properties, and their interlinked effects on the fundamental understanding of adhesive mixtures for inhalation. The knowledge gained is essential to ensure optimum blending and thereby controlled functionality of DPIs.

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“…However, little research has been performed on mannitol as a potential DPI drug delivery carrier [21].…”

Section: Introductionmentioning

confidence: 99%

Combined control of morphology and polymorph in spray drying of mannitol for dry powder inhalation

Lyu

Liu

Zhang

et al. 2017

Journal of Crystal Growth

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The morphology and polymorphism of mannitol particles were controlled during spray drying with the aim of improving the aerosolization properties of inhalable dry powders. The obtained microparticles were characterized using scanning electron microscopy, infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction and inhaler testing with a next generation impactor. Mannitol particles of varied -mannitol content and surface roughness were prepared via spray drying by manipulating the concentration of NH 4 HCO 3 in the feed solution. The bubbles produced by NH 4 HCO 3 led to the formation of spheroid particles with a rough surface. Further, the fine particle fraction was increased by the rough surface of carriers and the high -mannitol content.Inhalable dry powders with a 29.1 ± 2.4% fine particle fraction were obtained by spray-drying using 5% mannitol (w/v)/2% NH 4 HCO 3 (w/v) as the feed solution, proving that this technique is an effective method to engineer particles for dry powder inhalation.

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Influence of Batch Cooling Crystallization on Mannitol Physical Properties and Drug Dispersion from Dry Powder Inhalers

Cited by 28 publications

References 35 publications

The influence of agitation sequence and ionic strength on in vitro drug release from hypromellose (E4M and K4M) ER matrices—The use of the USP III apparatus

The influence of agitation sequence and ionic strength on in vitro drug release from hypromellose (E4M and K4M) ER matrices—The use of the USP III apparatus

On the effects of blending, physicochemical properties, and their interactions on the performance of carrier-based dry powders for inhalation — A review

Combined control of morphology and polymorph in spray drying of mannitol for dry powder inhalation

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