dry powder aerosols

DPI by JENISHA TIMBADIYA JP

1. Innovation in aerosols Prepared by ; Jenisha Timbadiya (25) Topic: Dry powder inhaler Atmiya institute of pharmacy

2. Dry powder drug delivery There are many route of administration but oral is more preferrable ‘cause it’s non-invasive, convenient & painless so orally inhaled therapy have been developed. Instead of giving dry powder doses like tablets & capsules orally, inhalation of those dry powder doses is more better as it not required diffusion, absorption, metabolism it will directly absorbed in blood through lung tissue. Many advantages of drug delivery by inhalation like large surface area of lung provides efficient drug absorption Inhalation of dry powder is simple & convenient & gives quick action of drug can be obtained

3. Dry powder inhaler: introduction DPIs are devices through which a dry powder formulation of an active drug is delivered for local or systemic effect via the pulmonary route DPIs are used to treat respiratory diseases such as asthma, COPD, bronchitis etc. For inhalation dry powder particles must be sized less than 5µm whereas for systemic effects particle size of less than 2µm is needed for drug deposition in the small peripheral airways.

4. HISTORY In 1956 MDI was invented for asthma Inhalation of medication since 1950s In 1967 DPI started to use In 1988 in DPI multidose device TURBUHALER was introduced

5. An ideal DPI Effective dosing Targeted & optimized delivery Operable at low inhalation flow rates Uniform dose Effective device In process controls for quality Good enviornmental production Compact, portable, cheap & reusable Easy to use

6. Factors to be considered to improve dry powder drug delivery through inhalation: Powder production/powder properties Powder formulation Dry powder inhaler device .

7. Powder properties: Particle size: generally 2-5µm for alveoli penetration max size 3 micron & not less than 1 micron for free flow Over micronised powder creates problems like improper powder flow & forms deagegated cloud pH Surface rotation Surface morphology & surface energy is important for free flowing & formation of segregation cloud Crystallinity & polymorphism Moisture content & hygroscopicity Polydispersity Surface area

8. Formulation of powder drug for DPI a) Active p’ceutical ingredient Therapeutic protein, insulin, drugs to treat bone disorders, vaccines Drugs for asthma & chronic obstructive pulmonary disease like β 2 adrenergic agonists, corticosteroids, cromones & anticholinergic) API of micron size formulated with or without carrier b) excepient To improve flow properties & to prevent agglomeration Ex. Lactose, glucose, mannitol

9. Currently, lactose is the only excipient used in DPIs. Lactose is highly crystalline & has the smooth surfaces & satisfactory flow properties desirable for a DPI carrier particle. One drawback of lactose is that it is a reducing sugar, which makes it incompatible with drugs that have primary amine moieties. Excipients are not always required, the Pulmicort , Astrazeneca ( Budesonide) Turbuhaler is an example of an excipient free formulation. Why lactose is used???

10. Principle of operation

11. Fate of inhaled drug: 1)Deposition in respiratory tract 2)Clearance mechanism: Dissolution Mucocillary clearance(MCC) Macrophage uptake Translocation

12. DPI device DPI design must be coordinated with the formulation of drug Performance of drug & reachness of drug to lungs not only depends on powder formulation but also on the inhaler device. Mouthpiece is critical parameter.

13. Classification of DPI device

14. 1)Single unit dose systems: Unit dose systems package drug powders into individual use package that contain a known qty of drug ex. Spinhaler , rotahaler , Handihaler , A erolizer a) S pinhaler : In it capsule is placed into a holder located on top of a propeller. The walls of capsule are pierced by two spears when the patient primes the device by sliding a cam. spinhaler TM

15. Spinhaler

16. b) R otahaler : Insert capsule into rotahaler Twist it to break the capsule Inhale deeply Several breath may be required. No coordination of aerosol required After use,empty gelatin capsule removed & replaced by another capsule

17. c) H andihaler

18. d) Aerolizer

19. 2)Multi dose reservoir devices Reservoir systems offer the advantage of variable dosing, generate less waste, are less expensive to manufacture & are simpler to use than unit dose systems. Maintaining a highly flowable drug powder in this system leads to greater drug formulation challenges. This contain a bulk supply of drug from which individual doses are released with each acutation . The first such inhaler to be develop was Turbuhaler . Other ex. Twisthaler , Easyhaler , Clickhaler , Accuhaler .

20. 1)loading dose: While loading, it must be in upright position. Twist the bottom colored grip fully to the right side, twist it back again to left. There will be sound of click. 2)inhaling the dose: Keep it in horizontal position. Inhale for 10 sec. There is window for dose indicator onto device. a) T urbuhaler

21. b) Twisthaler

22. c) Accuhaler / Diskus

23. 3)Multi-unit dose devices Multi unit dose DPIs utilizes individually prepared & sealed doses of drug. The first develop was aerohaler which contained six unit dose capsule each delivering one dose of drug. Ex. Aerohaler , Diskhaler

24. a) Aerohaler : To load: Lift up the mouthpiece to open Lift the magazine up slightly & turn it round in a clockwise direction until mark 6 lines up with the on the base. Push magazine down again Load the capsules into the magazine. Push the mouthpiece down until it clicks

25. To use: To inhale hold it upright. Push the button, on side of inhaler until it clicks, it pierces the capsule. Breath out, put mouthpiece in mouth, breath in as deeply as possible, remove aerohaler from mouth, hold breath for 10 sec, breath out. Turn the magazine for next dose. Reload magazine when all capsules have been used.

26. Aerohaler

27. b) Diskhaler / Rotadisk

28. Device drug 1) Rotahaler Albuterol/salbutamol, beclomethasone Handihaler Tiotropium Aerolizer Eformoterol 2) accuhaler /Discus Albuterol/salbutamol, beclomethasone , c Clickhaler Albuterol/salbutamol, beclomethasone Easyhaler Albuterol/salbutamol, Beclomethasone Turbuhaler Budesonide, Formoterol , Terbutaline 3) Aerohaler Fenoterol , Ipratropium bromide Diskhaler / Rotadisk Albuterol/salbutamol, Beclomethasone , Albuterol/salbutamol, beclomethasone

29. Current DPI producing brands Gold® Astra® Asmanex ® Seretide ® Relenza® Bochringer Ingelheim ® Symbicort ® Mankind®

30. Advantages of DPI Little or no patient coordination is required Convenient & easy to use Propellent free design as this is toxic in nature. Onset of action without need for absorption, digestion, circulation of drug because direct absorption from alveoli to blood for systemic effect Quick relief in case of bronchodilation Spacer is not required Higher lung deposition than pMDI .

31. Disadvantages of DPI Dependency on patient’s inspiratory flow rate. Device resistance & other design issues like mouthpiece is critical for inhalation. Not available world wide. More expensive than pMDI . Dose uniformity problems. Development & mfg are more expensive & complex. Most type are moisture sensitive. Humidity potentially causes powder clumping & reduced dispersal of fine particle mass. Need to reload capsule each time.

32. Apperance & colour Microscopic evaluation Microbial limits water/moisture content Assay(drug content determination) Particle size analysis Drug content per unit dose / dose delivery Average fill weight per capsule Impurities & degradation products Evaluation in DPI

33. Initially inhalation therapy was used only for pulmonary diseases like asthma. But from past few decades it is used in Cystic fibrosis, Chronic obstructive pulmonary disease as well as in systemic diseases like Irritable bowel syndrom , Schizophrenia, Migraine, Diabetes, Obesity Recent progress in non-pulmonary indications includes: Staccata ® filled by Loxapine – Schizophrenia – US A frezza ® - diabetes Inavir ® - influenza - Japan

34. References www.sciencedirect.com www.medscape.com Wikipedia.org Newman sp – aerosol drug delivery, deposition & clearance studies Mankind.co.in J. hickey – p’ceutical inhalation aerosol technology Remington – the science & practice of pharmacy C OPD at your fingerprint by John miles & J une robert

35. THANK YOU!!!!!