Natural Herbs
Natural Herbs
Natural Herbs
Review Article
RECENT ADVANCES IN PULMONARY DRUG DELIVERY SYSTEM: A REVIEW
SIRAJ SHAIKH*1, SAYYED NAZIM1, TARIQUE KHAN1, AFSAR SHAIKH1, MOHAMMAD ZAMEERUDDIN1, AAMER
QUAZI2
1 AliAllana College Of Pharmacy Akkalkuwa Dist Nandurbar425415, Maharashtra, India. 2K.T. Patil College of Pharmacy Osmanabad.
Maharastra, India. Email: [email protected].
Received: 01 July2010, Revised and Accepted: 23 July 2010
ABSTARCT
The lung has served as a route of drug administration for thousands of years. Now a day’s pulmonary drug delivery remains the preferred route for
administration of various drugs.
In this article, we summarize the rationale behind the advances of pulmonary drug delivery system. Pulmonary drug delivery is an important
research area which impacts the treatment of illnesses including asthma, chronic obstructive pulmonary disease and various other diseases.
Inhalation gives the most direct access to drug target. In the treatment of obstructive respiratory diseases, pulmonary delivery can minimize
systemic side effects, provide rapid response and minimize the required dose since the drug is delivered directly to the conducting zone of the lungs
.It is a needle free several techniques have been developed in the recent past, to improve the Quality of pulmonary drug delivery system without
affecting their integrity. This article focuses on recent advances in the technologies, devices, formulation and applications of pulmonary drug
delivery system.
Key words: Inhaler, Aerosol, Pulmonary drug delivery, Dry powder inhaler, Meter dose inhaler,nebulizer, Fine particle fraction.
INTRODUCTION Low velocity after generation
Pulmonary route have been used to treat various respiratory High concentration and rate of generation
diseases for centuries. Ancient inhalation therapies included the use
of leaves from plants, vapors from aromatic plants, balsams, and Highly reproducible characteristics
myhrr. However, around the turn of the 19th century, with the Low bioburden (solids) or sterile (liquids)
invention of liquid nebulizers, these early treatments developed into
legitimate pharmaceutical therapies. In the 1920 s adrenaline was ADVANTAGES OF PULMONARY DRUG DELIVERY
introduced as a nebulizer solution, in 1925 nebulizer porcine insulin
Inhaled drug delivery puts drug where it is needed.
was used in experimental studies in diabetes, and in 1945
pulmonary delivery of the recently discovered penicillin was It requires low and fraction of oral dose i.e. drug content of one 4 mg
investigated. steroids had been introduced in the mid 1950s for the tablet of salbutamol equals to 40 doses of meter doses.
treatment of asthma and nebulizers were enjoying widespread use.
In 1956 the pressured metered dose inhaler (pMDI) was introduced, Pulmonary drug delivery having very negligible side effects since
over the past 5 decades, helped by the advances in molecule design rest of body is not exposed to drug.
and drug discovery the pMDI has risen to become the main stay of
Onset of action is very quick with pulmonary drug delivery.
asthma treatment .1
Degradation of drug by liver is avoided in pulmonary drug delivery.
Over the decade certain drugs have been sold in compositions
suitable for forming drug dispersion for pulmonary delivery to treat In asthma and diabetes requires long term treatment if it is given by
various conditions in humans. Such pulmonary drug delivery pulmonary drug delivery safety is maximum because rest of body is
compositions are designed to be delivered by inhalation by the not exposed to drug.3
patient of a drug dispersion so that the active drug within the
dispersion can reach the lung. It has been found that certain CHALLENGES IN PULMONARY DRUG DELIVERY
drugs given by pulmonary route are readily absorbed through Low Efficiency of inhalation system
the alveolar region directly into blood circulation. Pulmonary
route possesses many advantages over other routes of Efficiency of presently available inhalation systems has generally too
administration for the treatment of specific disease states, low which is important challenge in pulmonary drug delivery.
particularly lung associated large protein molecules which degrade Optimum aerosol particle size is very important for deep lung
in the gastrointestinal conditions and are eliminated by the first pass delivery. Optimum particle size for deep lung deposition is 1‐5 mm.
metabolism in the liver can be delivered via the pulmonary route if Aerosol system should have to produce optimum size particles
deposited in the respiratory zone of the lungs. Devices used to because they are too small, they will be exhaled. If the particles are
deliver drug by pulmonary route area based on one of three too large, they affects on the oropharynx and larynx.
platforms pressurized metered dose inhaler, nebulizer and dry
powder .In the treatment of disease, aerosol administration Less drug mass per puff
represents a valuable means by which a therapeutic agent may be
To get adequate effect with the pulmonary drug delivery practical
delivered.2
delivery of many drug which require milligram doses but With most
IDEAL CHARACTERSTICS OF THERAPEUTIC AEROSOL existing systems, the total amount of drug per puff delivered to the
lower respiratory tract is too low less than 1000 mcg .
Contain a safe and efficacious drug.
Poor formulation stability for drug
Contain minimal quantities of inert excipients.
Most traditional small molecule asthma drugs are crystalline and, in
Monodisperse, small particle size the case of corticosteroids, relatively moisture resistant in the dry
Saikh et al.
Int J Appl Pharm , Vol 2, Issue 4, 2731
state. They are also rather stable in liquids as compared to most permanent and cleavable links in the agglomerate experiments on
macromolecules, which are unstable in the liquid state, amorphous, the release of ciprofloxacin from these agglomerates in vitro are
and highly moisture sensitive in the dry state. presented. Recent developments regarding the powder formulation
aim at a reduction of the adhesive and cohesive forces between the
Improper dosing reproducibility particles to increase the FPF.7
Following are reason for Poor dosing reproducibility like worsening RECENT ADVANCES IN PULMONARY DRUG DELIVERY DEVICES
of diseases’, problem in device, unstabality of formulation. To get
maximum dose reproducibility patient education play important Following types of inhalation devices are present
role. 1
Inhalation drug delivery system by‐ metered dose inhalers
RECENT ADVANCES IN PULMONARY DRUG DELIVERY INCLUDES
Inhalation drug delivery system by —dry powder inhalers
Recent Advances in technology of pulmonary drug delivery
Inhalation drug delivery system by ‐nebulizer
Recent advances in pulmonary drug delivery devices
A ) Inhalation drug delivery system by metered dose inhalers
Recent Advances in formulation of pulmonary drug delivery
A metered‐dose inhaler (MDI) is a complex system designed to
Recent Advances in applications of pulmonary drug delivery provide a fine mist of medicament, generally with an aerodynamic
particle size of less than 5 microns, for inhalation directly to the
Key concept responsible for advances in pulmonary drug airways for the treatment of respiratory diseases such as asthma
delivery and COPD.
Over the past 15 years, inhalation systems have been developed that Advances in MDI Technology and Use Enantiomer Preparations
make use of new technological concepts aiming for one or more of of Inhaled Drugs
the following improvements partly adapted from following key
concepts. There has been much interest in the differences in effects of
Enantiomer of many medications, and beta agonist adrenergic
Improvements regarding the fine particle fraction (FPF) bronchodilators have received much attention. Recently levo
salbutamol active enantiomer of salbutamol is present in market
Inhalation system that produces particles of 1‐5 mm size and fine which is free from termers and palpitation that seen in salbutamol.
particle fraction so that good deposition in to lungs. A high batch to Similarly that the (R)enantiomer of albuterol is mainly responsible
batch reproducibility of the FPF to reduce variability in lung for bronchodilator while the (S)‐enantiomer may stimulate airway
deposition.Monodisperse inhalation sysytem, to target the reactivity. Data suggest, however, that after aerosol delivery, the
deposition in the lung. systemic absorption for (R)‐albuterol is faster than for (S)‐albuterol
and that, conversely, the lung retention of (S)‐albuterol is longer,
Improvements that affect particle velocity and reduce
which may be detrimental.
coordination problems
Generic proliferation of devices and medications
To avoid oropharyngeal deposition, Systems that produces the
aerosol at a reduced velocity is preferred. Systems that not only Nowadays new MDI and nebulizer brands are introduced regularly
release the aerosol during the first 0.5 s of the inhalation but also in pharma market. Even for those who watch this field, it is not
generate the aerosol over a period longer than 1 s such type of unusual to hear a new, unfamiliar brand name regularly. One trend
system reduces coordination problems for the patient . coordination has been the move to generic MDIs and to over the counter
problems of patient is reduced by breath actuated systems. availability. These are introduced in the literature by comparing
them with well‐known older devices. Often, documentation that
Improvements that reducing the cost by increasing the patient generic brands or new devices are comparable to older ones is
compliance difficult to come by, so comparisons showing pharmacokinetic
To get above type of improvement following type of aerosol system equivalency are useful.
is selected Systems that are simple to use and robust, non fragile , New technologies to improve patient’s inhalation coordination
small and easy to carry and do not require electricity or pressurized with MDI
air.4
Spacers are used to improve patient coordination with MDI. Both
RECENT TECHNOLOGIES USED IN PULMONARY DRUG DELIVERY adults and children often have difficulty coordinating the inhalation
Particle engineering for pulmonary drug delivery effort with the timing of the aerosol puff. Evidence indicates
considerable intra and intersubject variability for the inhalation
Recent advances in inhalation therapy have sparked considerable technique. 8,9
biomedical interest in the development of novel particle
Flow gate valve technology in spacers
technologies for respiratory drug formulation. Introduction of new
potent medicines in various therapeutic areas such as asthma, Certain company s spacer present in market which is static free
chronic obstructive pulmonary disease (COPD) and various with valve mechanism which increases drug dose reaching to lungs.
infectious diseases has necessitated an accurate and consistent Valves opens during inhalation and closed during exhalation this
dosing with inhalation devices. There are many emerging inhalation ensures that the residual dose is retained in spacer for subsequent
products with new absorption mechanisms and/or rapid onset of inhalation3
action for systemic therapies. Controlled and sustained release with
composite particles is another applications used for ` for both local The autohaler modified form of pMDI
and systemic drug deliveries.5,6 The Autohaler TM is the first breath actuated or activated
Agglomerated vesicle technology for pulmonary drug delivery pressurized metered dose inhaler . Autoihaler solve the key problem
of the pressurized metered dose inhaler (pMDI) viz. coordination of
These particles are of multimicron sized chemically linked actuation with inhalation and does not rely on the patient's
agglomerates of core nanoparticles. The links between the inspiratory effort to aerosolize the dose of medication unlike dry
nanoparticles can be either permanent (e.g. carbonyl) or cleavable powder inhalers .Autohaler is modified form of pressurized metered
(e.g. disulfide or ester). Complex agglomerate structures can be dose inhaler. 3
achieved by scheduling the application of linker agents. The release
B) Inhalation drug delivery device by dry powder inhalers
rate of drugs from the assembly can be modulated by controlling the
extent of cleavage of the links. One envisions the structure of the Today there are essentially two types of DPIs, those that use drug
agglomerate during cleavage being controlled by the location of the filled into discrete individual doses, e.g., either a gelatin capsule or a
28
Saikh et al.
Int J Appl Pharm , Vol 2, Issue 4, 2731
foil–foil blister, and those that use a reservoir of drug that meters surface. The aerosol produced by an air jet nebulizer is generated
out doses when required. Both are now widely available around the when compressed air is forced through an orifice, an area of low
globe and are gaining broad acceptance. pressure is formed where the air jet exists. A liquid may be
withdrawn from a perpendicular nozzle (the Bernoulli Effect) to mix
Unit‐Dose ‐Devices Single‐dose powder inhalers are devices in with the air jet to form droplets. A baffle (or baffles) within the
which a powder containing capsule is placed in a holder. The capsule nebulizer is often used to facilitate the formation of the aerosol
is opened within the device and the powder is inhaled. The capsule cloud. Carrier air can be used to generate the “air jet.” alternatively,
residue must be discarded after use and a new capsule inserted for compressors may be used to generate the air stream. Nebulizers
the next dose used today for drug delivery to the respiratory tract and are
Multidose Devices ‐ Multidose device uses a circular disk that particularly useful for the treatment of hospitalized or
contains either four or eight powder doses on a single disk. This nonambulatory patients.13
typically would be treatment for one to two days. The doses are Recent developments in liquid aerosol technology combine the
maintained in separate aluminum blister reservoirs until just before advantages of MDIs and nebulizers is called metered dose liquid
inspiration. This device is a true multidose device, having 60 doses inhalers’ as we know that the CFC propellants were replaced by
in a foil–foil aluminum strip that is opened only at the point just HFAs in MDIs and the classical nebulizer area was extended with the
prior to patient inspiration.10,11 adaptive aerosol delivery (AAD) technology in the 90s of the past
New developments in dry powder inhalation technology century, several’ .These systems try to combine the advantages that
MDIs and nebulizers offer, and to get rid of the many disadvantages
Changes in the performance of the DPI can be achieved either they suffer from. The major advantage that all these systems aim for
through changes in the design of the device through changes in the is a reduced velocity of the aerosol. This feature is of paramount
powder formulation, or . described extensively, the forces governing importance because it will reduce oropharyngeal deposition and
the particle–particle interactions in the agglomerates and the forces increase the lung deposition. Liquid inhalers applying the concept of
playing a role in the deagglomeration process .Recent developments a low velocity aerosol are often referred to as ‘soft mist inhalers’.
regarding the powder formulation aim at a reduction of the adhesive Further developments in the field of wet nebulization aim at the
and cohesive forces between the particles to increase the FPF. generation of monodisperse aerosols ,the absence of propellants in
Supercritical fluid technology is applied to improve the surface the formulation by applying aqueous drug formulations, a
properties of the drug substance Large porous particles have reduction in the residual volume after nebulization and an
reduced inter‐particulate forces because of their low density, the improved portability compared with nebulizers.14
irregular surface structure and/or reduced surface free energy .
Moreover, these particles are claimed to have improved Depend upon generation of aerosol new technologies areclassified
aerodynamic behavior in the airways, whereas phagocytosis of the into four groups
deposited particles in the alveoli is reduced . In another approach, Systems that force the liquid through a nozzle ‐ Respimat , AERxTM,
smaller porous particles (3–5 mm) have been used to improve MedSpray
deagglomeration and lung deposition.
Systems that use a vibrating mesh or perforated plate ‐ Aerodose.
Changes in device technologies are few new developments really TouchsprayTM technology.
aim at an increase of the deagglomeration forces generated during
the inhalation. It is well known that if the more efficient the force is, Systems that use electrohydrodynamic breakup to generatethe
higher the FPF will be. A main classification parameters in the new aerosol‐ MysticTM (Battelle)
device developments is whether or not the powder deagglomeration
is power assisted (active devices) or depends on the kinetic energy Systems that apply condensation to generate the aerosol.4
of the inhalation flow generated by the patient (passive devices). RECENT ADVANCES IN FORMULATION OF PULMONARY DRUG
Regarding the passive devices, recently two DPI devices were DELIVERY
introduced that apply impaction forces for the generation of the
aerosol. 12 Effective inhalable medication are produced by drug formulation.
Formulation stability is another challenge in producing pulmonary
Airclassifier technology in devices
drug delivery. Formulation is responsible for keeping drug
This is another most important technology used in recent devices for pharmacologically active, it must be efficiently delivered into the
pulmonary drug delivery. The inhaler contains a classifier (cyclone) lungs, to the appropriate site of action and remain in the lungs until
chamber in which high inertial forces are applied onto the rotating the desired pharmacological effect occurs. Depending upon disease
particles. Moreover, the action of these forces on the larger condition effective formulation release drug, such as insulin for
agglomerates is sustained because they remain in the classifier for a diabetes, must be deposited in the lung periphery to ensure
certain period of time, which can be controlled by the classifier maximum systemic bioavailability. . Thus, a formulation that is
design and by the choice of carrier‐size fraction. Air‐classifier retained in the lungs for the desired length of time and avoids the
technology system one contains a cyclone chamber for particle clearance mechanisms of the lung may be necessary. Research into
deagglomeration. Modified form of Airclssifier technology is dry powder formulations has been an area of growth in recent years
multiple air‐classifier technology. and will be the focus of this section. Various techniques are used to
made advances in dry powders formulation for inhalation involves
Multiple airclassifier technology either ,micronization via jet milling, precipitation, or spray drying
In this technology multiple classifier chambers are placed in a using various excipients, such as lipids and polymers, or carrier
parallel arrangement, which further increases the dose that can be systems like lactose.
aerosolized. Another interesting point in this development is that
Lactose carrier systems
the authors managed to develop a disposable DPI. The concept of a
disposable inhaler is interesting because it reduces the chance of Recent advances in inhalation therapy have sparked considerable
microbial contamination. biomedical interest in the development of novel particle
technologies for respiratory drug formulation .The cohesive
C) Inhalation drug delivery devices by nebulizer
powders with poor flow arises if the surface electric forces
Mainly there are two general types of nebulizer systems, the associated with the particles exceed the gravitational force acting
ultrasonic and the air jet. In ultrasonic nebulizers, ultrasound waves upon them’. To overcome this problem, the drug is blended with a
are formed in an ultrasonic nebulizer chamber by a ceramic coarse carrier system (30–100 µm), such as lactose. At present,
piezoelectric crystal that vibrates when electrically excited. These marketed dry powder inhalers contain either the drug alone or
set up high energy waves in the solution, within the device chamber, mixed with a bulk carrier, usually lactose (α‐lactose monohydrate).
of a precise frequency that generates an aerosol cloud at the solution Lactose has an established safety profile and improves the flow
29
Saikh et al.
Int J Appl Pharm , Vol 2, Issue 4, 2731
properties of the formulation necessary for reproducible filling and therapy and as a method of delivering therapeutic agents to the
promoting dosing accuracy alveolar surface for the treatment of systemic diseases.
Liposomes Sustained release from a therapeutic aerosol can prolong the
residence of an administered drug in the airways or alveolar region,
Liposomes, as a pulmonary drug delivery vehicle, have been studied minimize the risk of adverse effects by decreasing its systemic
for years and used as a means of delivering phospholipids to the absorption rate, and increase patient compliance by reducing dosing
alveolar surface for treatment of neonatal respiratory distress frequency. A sustained‐release formulation must avoid the clearance
syndrome. More recently, they have been investigated as a vehicle mechanisms of the lung, the mucociliary escalator of the conducting
for sustained‐release therapy in the treatment of lung disease, gene airways and macrophages in the alveolar region.
Table 1: Shows the advantages and disadvantages of the different technologies of dry powder inhalaton4
Name of technology Disadvantage
Advantages
For particale medication of powder Smooth surface with decreased cohesive and adhesive Difficult to scale up and Costly technology
formulation in dry powder inhalers. forces, pure highly crystalline drug obtained,increases .
Supercritical technology FPF.Decreases batch to variability
Pulmosphere and large porus particale improved processing , deagglomeration and improved Expensive technology and non approved
technology of powder formulation in dry aerodynamic behavior excipients necessary.
powder inhalers.
Air classifier technology and eclipse Economic simple high FPF possible and high sustaines Requires adequate formulations and
technology in passive devices. deagglomeration forces possible. risk of polution of system.
pulmonary inhaler, aspirair,spiros Mainly studied with insulin dependant on battery and losses in
technology in active devices. and holding chamber allowed for slow inhalation. holding chambers
Table 2: Show the advantages and disadvantages of the different technologies of metered dose liquid inhalers
Name of the Technology Advantage Disadvantage
AeroDose (Aerogen) Significant improvement Comlex and expensive electronics in the device
(2) eFlow (Pari) compared with MDI nebulizer and Well‐ and dependent on battery or external energy
(3) Omron NE‐U03, NE‐U22 controlled monodisperse aerosol source
Tecchnologies in vibrating mesh and Aerosol generation independent of
nebulizers of metered dose liquid inhaler inspiratory flow rate
1) AERx (Aradigm) I. Significant Expensive and complex device
(2) MedSpray Tecchnologies in Capillary wave improvement compared
break‐up nebulizers of metered dose liquid with MDI and nebulizer in both
inhaler technologies and both rechologies
monodisperse aerosol
II. No coordination Dependent on
problems for patient seen with AERX Electronics
Technology
Low shear forces in High pressure on liquid
nozzle with minimum
resistance, and therefore,
low pressures and Complete dose
Large porous particles limited amount of research has been published in this area, the
sustained‐release profiles achieved with corticosteroids appear
Pulmospheres are the new type of aerosol formulation is the large promising. However, the toxicity of this type of formulation has not
porous hollow particles,. They have low particle densities, excellent yet been established for lung delivery.14,15,16,17,18,19
dispersibility and can be used in both MDI and DPI delivery systems.
These particles can be prepared using polymeric or nonpolymeric Advances in propellants used in pulmonary drug delivery
excipients, by solvent evaporation and spray‐drying techniques. devices
Pulmospheres are made of phosphatidylcholine, the primary
component of human lung surfactant. The large size of Recently HFA propellants are a new alternative for CFC propellants
Pulmospheres allows them to remain in the alveolar region longer in pulmonary drug delivery devices. Generally the higher vapor
than their nonporous counterparts by avoiding phagocytic pressures of the HFAs (particularly 134a) have the potential to
clearance. After intratracheal administration into rats, only 8% and generate aerosols of higher quality than the “old” CFC formulations.
12.5% of macrophages contain Pulmospheres particles immediately However, except in a few notable instances, potential product
and 48 h after inhalation, respectively, compared with 30% and 39% improvements have been sacrificed for development costs and time
of macrophages containing nonporous particles during a similar as per market need.20
time interval. RECENT TREND IN APPLICATIONS OF PULMONARY DRUG
Biodegradable polymers DELIVERY
30
Saikh et al.
Int J Appl Pharm , Vol 2, Issue 4, 2731
Treatment of Migraine 4. Henderik W. Frijlink, Anne H. de Boer, “Trends in the
technology‐driven development of new inhalation devices”,
Nicotine Aerosol for Smoking Cessation drug discovery today.technology 2005; vol.2.no.1.
Aerosols for Angina. 5. Albert H. L. Chow,1,4 Henry H. Y. Tong,2 Pratibhash
Chattopadhyay,3 and Boris Y. Shekunov, “Particle Engineering
Aerosol Vaccination. for Pulmonary Drug Delivery,” Pharmaceutical Research, ,
March 2007; Vol. 24, No. 3,p.411‐433.
Alpha 1 Antitrypsin
6. David A. Edwards, Abdelaziz Ben‐Jebria, and Robert Lange
Aerosols in Transplantation “Recent advances in pulmonary drug delivery using large,
porous inhaled particles,” J Appl Physiology 85: 1998; Vol. 85,
Pulmonary arterial hypertension Issue 2, p.379‐385.
7. Rohan Bhavane, Efstathios Karathanasis, Ananth V.
Acute Lung Injury
Annapragada, “Agglomerated vesicle technology”: a new class
Surfactant Aerosol of particles for controlled and modulated pulmonary drug
delivery, Journal of Controlled Release 2003;p 15– 28.
Gene Therapy via Aerosol 8. Paul J. Atkins and Timothy M. Crowder, Paul J. Atkins and
In Cancer chemotherapy Timothy M. Crowder, “The Design and Development of
Inhalation Drug Delivery Systems”, modern pharmaceutics by
Pentamidine Aerosol Marcel Dekker p.1‐31.
9. Manfred Keller, “Innovations and perspectives of metered dose
Amphotericin B inhalers in pulmonary drug delivery”, international journal of
Gentamycin aerosol pharmaceutics 186 (199) 81‐90.
10. Costas Kaparissides, Sofia Alexandridou, Katerina Kotti and
Ribavirin Aerosol Sotira Chaitidou, “Recent advances in novel drug delivery
systems”, azojono, 2006.
Zanimivir R/C with revolizer for swine flue. 11. Paul J. Atkins and Timothy M. Crowder, Paul J. Atkins and
Aerosols used in clinical investigations of disease Timothy M. Crowder, “The Design and Development of
Inhalation Drug Delivery Systems”, modern pharmaceutics by
Inhaled Drug Delivery for Tuberculosis Therapy Marcel Dekker page no.1‐31.
12. Manfred Keller, “Innovations and perspectives of metered dose
Pulmonary delivery of lower molecular weight Heparin.
inhalers in pulmonary drug delivery”, international journal of
Controlled delivery of drugs to lungs pharmaceutics 186 (199) 81‐90.
13. Dr Henrik LuessenTytonis BV,” Pulmonary drug delivery new
Pulmonary delivery of drugs for bone disorders perspectives on inhalers and inhalables” ONdrugDelivery Lt,
Aug 2007
Pulmonary delivery of opioids as pain therapeutics
14. O.N.M.CALLION “Jet nebulizer for pulmonary drug deliver”,
CONCLUSION International journal of pharmaceutics 1996, p. 1‐11.
15. P.P.H. Le Brun, A.H. de Boer, H.G.M. Heinemann and H.W.
There have been a number of significant achievements in frijlink “A review of the technical aspects of drug nebulization”,
technologies to express and deliver drugs by pulmonary route. Pharm World Sci 2000;22(3) Kluwer Academic Publishers
Improvements in the aerosol’s velocity, particle size, or moment of p.75‐81.
release have been achieved. But drug administration via pulmonary 16. N R Labiris and M B Dolovich, Pulmonary drug delivery. “Part
route is a difficult and complex process, comprising not only aspects II: The role of inhalant delivery devices and drug formulations
from technology but also from physiology, clinical application or in therapeutic effectiveness of aerosolized medications”, Br J
patient use.. This shows that for different diseases or even for each Clin Pharmacol. 2003 December; 56(6): 600–612.
individual drug, the required conditions for optimal administration 17. Anthony Moran astec project ltd “next generation of
differ substantially and that a perfect inhaler (plat‐form) suitable for automated pulmonary drug delivery system”, ONdrugDelivery
all types of drugs and diseases is a fiction. Lt, Aug 2007 .
Advantages of DPIs such simple and cheap devices, their robustness, 18. Hao‐Ying Li, Peter C. Seville “Novel PMDI formulations for
portability, easy of use as high FPF but systems that can disperse pulmonary delivery of proteins, International Journal of
larger amounts of powder (upto 50 mg) within one breath is Major Pharmaceutics,” 2009 ijp, page no 1‐6.
challenges that remain for dry powder inhalation. To maintain 19. Kathryn Senior, “New technology for pulmonary drug delivery”,
stability of powder formulation is another challenge associated with PSTT Vol. 3, No. 8 August 2000.
DPI. 20. F. Charles Hiller, Therapeutic Aerosols: “An Overview froma
Clinical Perspective”, modern pharmaceutics marcelDekker
As compare to classic nebulizers or MDIs the new liquid inhalation 2004 ;p.1‐31.
systems are certainly better option but many liquid aerosol
generation systems require an external energy source and contain
complex electronics. Due to this there is increase failure risk and
reduce the freedom of the patient. Further relevant aspects are the
dependency of the device’s performance on the physicochemical
characteristics of the liquid formulation . Advancements in
pulmonary drug delivery should not only focus on only one
technological aspects, but also need to focus on other aspects.
REFERENCES
1. Michael T. Newhouse, “Encyclopedia of Pharmaceutical
Technology”, second edition, Dekker, New York Informa
Healthcare USA, 2000;19:1279‐1285.
2. Derek Ivan Daniher, Jesse Zhu, Review on “dry powder
platform for pulmonary drug delivery”,
www.sciencedirect.com, Particuology 2008;225–238.
3. www.cipladoc.com
31