Process for Overcoming Drug Retention in Hard Gelatin Inhalation Capsules

Saim, Said; Horhota, Stephen T.

doi:10.1081/ddc-120003855

Cited by 12 publications

(25 citation statements)

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“…Due to the ease and availability of capsule filling, DPIs use hard gelatin or hypromellose capsules as pre-metered monodose unit systems [25]. Capsule activation is achieved by shear-force opening, needle-piercing, or cutting of the capsules.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in capsule-based dry powder inhaler technology

Lavorini

Pistolesi

Usmani

2017

Multidiscip Respir Med

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Pulmonary drug delivery is currently the focus of accelerated research and development because of the potential to produce maximum therapeutic benefit to patients by directly targeting drug to the site of pathology in the lungs. Among the available delivery options, the dry powder inhaler (DPI) is the preferred device for the treatment of an increasingly diverse range of diseases. However, because drug delivery from a DPI involves a complex interaction between the device and the patient, the engineering development of this medical technology is proving to be a great challenge. Development of DPI systems that target the delivery of fine drug particles to the deeper airways in the lungs using a combination of improved drug formulations and enhanced delivery device technologies means that each of these factors contributes to overall performance of the aerosol system. There are a large range of devices that are currently available, or under development, for clinical use, however no individual device shows superior clinical efficacy. A major concern that is very relevant in day-to-day clinical practice is the inter- and intra-patient variability of the drug dosage delivered to the deep lungs from the inhalation devices, where the extent of variability depends on the drug formulation, the device design, and the patient’s inhalation profile. This variability may result in under-dosing of drug to the patient and potential loss of pharmacological efficacy. This article reviews recent advances in capsule-based DPI technology and the introduction of the ‘disposable’ DPI device.

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Section: Introductionmentioning

confidence: 99%

Recent advances in capsule-based dry powder inhaler technology

Lavorini

Pistolesi

Usmani

2017

Multidiscip Respir Med

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“…However, this effect is reduced significantly as the level of lubricant increases to greater than 90 mg/kg MO lubricant per capsule. This results in a smooth inner surface of the capsule with less mountain and valleys (see Section 3.2) as there is less adhesion during the removal from the moulding pins, and hence, reduction in contact between particles and crevices (Ibrahim et al, 2000;Saim and Horhota, 2002).…”

Section: Resultsmentioning

confidence: 93%

“…The high salbutamol retention in low lubricant capsules occurred, because during the removal of the capsules from the mould pins there is a high degree of adhesion that causes roughness, which can be seen by the mountain and deep valleys, as shown by AFM (see Section 3.2). Hence during inhalation the salbutamol particles become entrapped or lodged within these peaks and crevices (Saim and Horhota, 2002). However, this effect is reduced significantly as the level of lubricant increases to greater than 90 mg/kg MO lubricant per capsule.…”

Section: Resultsmentioning

confidence: 98%

“…Capsules cannot be manufactured without this lubricant (Jones, 2008). However, a search of the literature only shows one study investigating the influence of the amount of mould lubricant on the internal surfaces of capsules in relation to the aerosolization properties of powders from a capsule based DPI (Saim and Horhota, 2002). Furthermore, this study relates to gelatin capsules and not HPMC.…”

Section: Introductionmentioning

confidence: 94%

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Investigation on the aerosol performance of dry powder inhalation hypromellose capsules with different lubricant levels

Saleem

Dı́ez²,

Jones³

et al. 2015

International Journal of Pharmaceutics

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HPMC capsules are made by a dipping process and a surface lubricant for the mould pins is an essential processing aid for removing dried capsules shells. For the purpose of this study, the level was determined by quantifying methyloleate (MO) a component found in the lubricant but not in the hypromellose capsules. Here we investigated the influence of the lubricant, low (10.81 μg/capsule=60 mg/kg MO), medium (15.97 μg/capsule=90 mg/kg MO) and high (23.23 μg/capsule=127 mg/kg MO) content on powder (binary mixture of salbutamol: lactose, 1:50 w/w) aerosolization properties was investigated. Results indicated significantly lower emitted dose from capsules with 60 mg/kg MO. Furthermore, the 90 and 127 mg/kg MO level of lubricant capsules produced almost double the Fine Particle Dose & Fine Particle Fraction compared with the low level of lubricant. The data indicates that lubricant level within capsules has an influence on deposition profiles and amount of drug remaining in capsule and inhaler device after actuation. It is suggested lubricant levels greater than 60 mg/kg MO per capsule are required to minimise powder retention within capsules and maximise deposition profiles. AFM (atomic force microscopy) data suggest that internal surface roughness may be related with this phenomena.

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“…Several papers have described the influence of ILC on aerosolization [12,13]. The reference [13] showed that there is an optimum ILC range to obtain good powder release from capsules as measured by their emitted dose and fine particle fraction [13].…”

Section: Introductionmentioning

confidence: 99%

Statistical tools and control of internal lubricant content of inhalation grade HPMC capsules during manufacture

Ayala

Dı́ez²,

Gassó

et al. 2016

International Journal of Pharmaceutics

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Elsevier Ayala, G.; Diez, F.; Gasso Matoses, MT.; Jones, BE.; Martin-Portugues, R.; MartinPortugues, R.; Ramiro-Aparicio, J. (2016) AbstractPulmonary delivery is being becoming a popular route for delivering active pharmaceutical ingredients that cannot be administered through by the standard oral route, as well as offering an improved alternative to the parenteral route. The use of hard capsules in dry powder inhalers (DPIs) to deliver formulations to the lung has been in use since 1970, and recently there has been an interest in changing from metered-dose devices to capsulebased ones because they are simple to formulate, cheap to manufacture, and patient-friendly. The original inhalation grade hard capsules were made from gelatin, which becomes brittle when exposed to low humidities. Inhalation grade hypromellose (HPMC, carrageenan gelling agent) has been developed in the last few years to overcome come this problem and has been shown to have better aerosolization properties. Hard capsules are made by a dipping process in which a surface lubricant is an essential processing aid for removing dried capsule shells from the manufacturing pins. This lubricant has been shown to have an effect on powder retention in capsules that are used for the inhalation of medicines. The capsule manufacturing process depends on many factors. The response is a function giving the the internal lubricant content (ILC) from 0 to 48 hours. Two of them were chosen by experts in order to evaluate their influ- Additionally we want to know if the mean ILC is between the tolerance limits. A bootstrap confidence region is used to estimate local confidence regions of the response.

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Process for Overcoming Drug Retention in Hard Gelatin Inhalation Capsules

Cited by 12 publications

References 1 publication

Recent advances in capsule-based dry powder inhaler technology

Recent advances in capsule-based dry powder inhaler technology

Investigation on the aerosol performance of dry powder inhalation hypromellose capsules with different lubricant levels

Statistical tools and control of internal lubricant content of inhalation grade HPMC capsules during manufacture

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