Determination of physical and chemical stability in pressurised metered dose inhalers: potential new techniques

Ooi, Jesslynn; Traini, Daniela; Boyd, Ben J.; Gaisford, Simon; Young, Paul M.

doi:10.1517/17425247.2015.1046834

Cited by 7 publications

(3 citation statements)

References 76 publications

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“…MDI formulations are prepared either by dissolving the drug into the HFA (such as HFA 134a and HFA 227) if it has sufficient solubility in the HFA, or using a co-solvent, usually ethanol, to increase the solubility of the drug in the HFA. In case that the drug has no solubility in the HFA, it is prepared as a micron-sized suspension in HFA (Pritchard, 2001; Ooi et al., 2015). Solution MDI formulations are relatively easy to be formulated in comparison to suspension formulations which suffers from tendency to flocculate and have a potential for physical instability (Khale & Bajaj, 2011) although they were reported to reduce bad tastes of the drug (Hickey, 2002).…”

Section: Introductionmentioning

confidence: 99%

In-vitro and in-vivo respiratory deposition of a developed metered dose inhaler formulation of an anti-migraine drug

Abdou

Kandil²,

morsi

et al. 2019

Drug Delivery

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Enhancement of zolmitriptan bioavailability through development of micronized zolmitriptan pressurized metered dose inhaler (MDI) as an alternative to its traditional drug delivery systems. A reversed phase HPLC method for zolmitriptan determination was developed and evaluated. Micronized zolmitriptan MDI formulations were prepared using two different propellants. The prepared formulations were evaluated for mean shot weight, drug content, and leakage rate in addition to in-vitro deposition using next generation impactor where mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), fine particle dose, fine particle fraction (FPF), emitted dose (ED), and dispersibility were determined. The selected formulation was evaluated for in-vivo bronchial absorption in rats. The physicochemical characters of the prepared formulations were found to be dependent mainly on the vapor pressure of the used propellant. MDI formulation prepared with HFA 134a propellant was found to have the lowest MMAD (3.47 ± 0.65) with GSD of 2.3 ± 0.4. It also had the highest FPF (41.9), ED (89.26 ± 2.35) with dispersibility of 46.9%. This formulation, when applied to rats, resulted in faster T max (27 ± 5 min) with higher C max (1236 ± 116 ng/mL) and AUC (0-12) (3375 ± 482 ng/mL·h) over the oral tablet. Its relative bioavailability was 72.7% which was 1.25 times higher than the oral tablet relative bioavailability. Zolmitriptan MDI formulation was developed using micronized zolmitriptan powder without further modification or particle engineering. The developed formulation using HFA 134a propellant could be favorable alternative, with enhanced bioavailability, to zolmitriptan oral tablet for acute migraine treatment.

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Section: Introductionmentioning

confidence: 99%

In-vitro and in-vivo respiratory deposition of a developed metered dose inhaler formulation of an anti-migraine drug

Abdou

Kandil²,

morsi

et al. 2019

Drug Delivery

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“…They are breath-synchronized devices, designed to time the pace of inspiration with the release of the dose from the inhaler. With the goal of having an integrated dose tracker, a soft triggering mechanism, and the capacity to activate at low inspiratory flow rates, a new generation breath-actuated pMDI has been devised [43]. Another relatively new breath-activated pMDI, the K-haler device uses a special "kinked-hose valve technology" and delivers lower, more consistent plume force than a normal pMDI in addition to fine particles and pulmonary deposition rate.…”

Section: Pmdimentioning

confidence: 99%

Amelioration in Approaches for Enhanced Pulmonary Drug Delivery

CHOUDHARY,

PATIL

2023

Asian J Pharm Clin Res

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Pulmonary disorders including asthma, chronic obstructive pulmonary disorder (COPD), cystic fibrosis, and other severe conditions like cancer have indeed made pulmonary drug delivery systems, both, an area of interest as well as concern. The mortality rate, around 8%, has enabled researchers to develop novel technologies for efficient drug delivery and reduced side effects. As the drug delivery through inhalation involves two major influencing factors, that is, formulation type and the device used for inhalation, various strategies have been designed with an intent to upgrade the existing drug formulations and devices used. Apart from this, various targeting strategies including gene therapy and magnetic targeting so as to improve the target specificity of the administered drug in the regions of the pulmonary system have been developed. In spite of these advancements, pulmonary drug delivery appears to be challenging in terms of formulation design and animal model design as well as lack of availability of FDA-approved excipients for inhalation. Persistent efforts have been made by the researchers in combining various strategies to negate the drawbacks/limitations of pulmonary drug delivery so as to develop a drug delivery system with improved efficacy and negligible adverse effects.

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“…Satisfactory content uniformity is an important factor to ensure dosage consistency for pMDIs. The sizespecific particle growth in suspension pMDIs associated with Ostwald ripening phenomenon will induce physical stability issues (21). Moreover, the preparation process of solid particles is complicated and tends to damage peptides structures.…”

Section: Introductionmentioning

confidence: 99%

Enhancing Stability of Exenatide-Containing Pressurized Metered-Dose Inhaler Via Reverse Microemulsion System

Huang

et al. 2018

AAPS PharmSciTech

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The dispersibility and stability issues of peptide drugs during preparation and storage hinder the widespread adoption of pressurized metered-dose inhaler (pMDI). This study aimed to develop a reverse microemulsion (RM) of exenatide (EXE) pMDI through a liquid-based bottom-up method, thus to overcome the stability issue of peptide drugs encountered in traditional top-down methods, such as milling down and high-pressure homogenization. In this study, Pluronic® L64 (L64) was chosen as a surfactant to prepare the EXE-RM pMDI formulations with the assistance of ethanol. The results showed RM possessed a particle size of 123.80 ± 2.91 nm with 0.121 ± 0.024 PdI and a satisfied fine-particle fraction of 41.30 ± 3.73% measured by a next-generation impactor. In addition, the dispersion stability of RM pMDI was maintained after storage at 4 °C for 50 days. The secondary structure of EXE was maintained during the preparation process. Moreover, the results indicated that L64 was compatible with cells and could improve the penetration of EXE through cell monolayers. Through the liquid-based bottom-up method, EXE-RM pMDI was successfully prepared and exhibited favorable stability and aerodynamic performance. This study offers a preparation strategy to enhance the stability of peptides in pMDIs.

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Determination of physical and chemical stability in pressurised metered dose inhalers: potential new techniques

Cited by 7 publications

References 76 publications

In-vitro and in-vivo respiratory deposition of a developed metered dose inhaler formulation of an anti-migraine drug

In-vitro and in-vivo respiratory deposition of a developed metered dose inhaler formulation of an anti-migraine drug

Amelioration in Approaches for Enhanced Pulmonary Drug Delivery

Enhancing Stability of Exenatide-Containing Pressurized Metered-Dose Inhaler Via Reverse Microemulsion System

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