Project Title :
Pressurized metered dose inhalers technology
Student Name : Eman Gamal MokhtarStudent University Number:
Submitted to :
Dr. Eman Zamily
MSc Module : Physical Pharmacy
The pressurized metered-dose inhaler (pMDI) is accurate, highly effective, extremely safe and allowing multi-dose delivery to asthmatic patient.
The components of the pMDI device (propellants, formulation, metering valve, and actuator) all play roles in the formation of the spray, and in determining drug delivery to the lungs.
Modern pMDI devices, which contain non ozone-depleting propellants, should allow inhalation therapy to extend well for a variety of treatment indications.
Modern pMDI devices, which have a valve holding chamber plus a mouthpiece or mask markedly improved the ease, speed and reliability of aerosol therapy for reversible airflow obstruction in adults, children and infants.
pMDI, effective and easily accessible when patients are away from home for the treatment of reversible airflow obstruction.
-19050-85725 Table of Content
TABLE of CONTENT 3
1. INTRODUCTION 4
2. DISCUSSION 5
2.1. First subsection 5
2.2. First subsection 5
3. CONCLUSION 6
4. REFERENCES 7
-38100-10477500 1. Introduction
In the first half of the 20th century, inhaled drugs for the treatment of asthma and chronic obstructive pulmonary disease (COPD) were mostly delivered via hand-held,
squeeze-bulb nebulizers. These devices were fragile, and since the dose varied with hand pressure, they did not provide consistent drug delivery (Thiel, 1996).
Riker Laboratories set out in the mid-1950s to develop formulations of bronchodilator drugs in pressurized containers, providing greater convenience and a more reliable dose.
In June of 1955, the first clinical trials at the Long Beach Veterans Administration Hospital showed these first pMDIs to be effective, and new drug approvals filed in January of 1956 were approved by March of the same year ( Lenney et al., 2000).
In 1957, a suspension of micronized drug in propellant with a surfactant was substituted for the original bronchodilators. It is interesting that, although the suspensions proved to be more effective in all pulmonary measurements, many of the previous pMDI users complained that they were not getting as much medication.
Apparently, patients missed the taste of the alcohol present in early solution formulations, which they associated with active medication. This era represented much of the technologic innovation we are familiar within the current chlorofluorocarbon (CFC)- propelled pMDIs. Soon thereafter, the Kefauver amendments to the food and drug laws required more complex new drug approval submissions and clinical trials. This radically curtailed innovative development of pMDI technology for the next 40 years(Smith et al.,1998).
Molena and Rowland theory that CFCs were contributing to ozone depletion led to a ban of CFCs in common aerosol products (Molina and Rowland, 1974).
By the end of the decade the ozone depletion theory was falling into disrepute, and interest in alternative propellants such as perfluoropropane was limited by the expense of toxicity testing and clinical testing (Fink et al., 1998).
The first alternative propellant compound to enter full term industrial toxicity tests was hydrofluoroalkane (HFA) (tetrafluroethane), which appeared to be a promising replacement for CFC (Dolovich and Leach , 1999)
These propellants have physicochemical properties similar to CFCs used in pMDIs.
Dolovich M, Leach C. Drug delivery devices and propellants, In:Busse W, Holgate S, editors. Asthma and rhinitis. Oxford: Blackwell Science; (1999).
Fink JB, Wilkes W, Dhand R, Fahey PJ, Tobin MJ. A new method to characterize the effects of spacers and holding chambers on poor hand-breath coordination during MDI use. (abstract) Respir Care;43(10):873 (1998).
Lenney J, Innes JA, Crompton GK. Inappropriate inhaler use: assessment of use and patient preference of seven inhalation devices. Respir Med;94(5):496–500 (2000).
Molina MJ, Rowland FS. Stratospheric sink for chlorofluoromethanes: chlorine atom catalysed destruction of ozone. Nature; 249:810–812 (1974).
Smith KJ, Chang H-K, Brown KF. Influence of flow rate on aerosol particle size distributions from pressurized and breath actuated inhalers. J Aerosol Med;11(4):231–245 (1998).
Thiel CG. From Susie’s question to CFC free: an inventor’s perspective on forty years of MDI development and regulation. In: Dalby RN, Byron PR, Farr SJ, editors. Respiratory drug delivery V. Buffalo Grove: Interpharm Press; 115–123 (1996).