BPH 5.1 PHARMACEUTICAL POWDERS PCE 410.pptx

Pharmaceutics

1. PHARMACEUTICAL POWDERS

2. INTRODUCTION WHAT ARE POWDERS Powders - Collection of solid, loose, dry particles of same or different chemical compositions having equivalent diameters of < 1000 µm Powder as dosage form - administrable formulation in which drug powder has been mixed with other powdered excipients to produce a powdered final product T w o group s o f powder s ar e recognized b y pharmacopoeia s – ora l powder s an d topica l powders . The function of the added e x cipients depends on th e intende d us e o f th e product . F o r example , colou r ing , flavouring , sweetening , an d tast e maskin g agents may be added to powders for oral use.

3. Advantages of Powdered Products as Dosage Forms 1. Solid preparations are more chemically stable than liquid ones. The shelf life of powders for antibiotic syrups, for example, is 2–3 years, but once they are reconstituted with water it is only 1–2 weeks. The instability observed in liquid preparations is usually the primary reason for presenting some injections as powders to be reconstituted just prior to use. 2. P owders are a convenient form in which to orally administer drugs with a high dose. The dose of Compound Magnesium T risilicate Oral P owder is 1 g to 5 g and, although it is feasible to manufacture tablets so as to supply this dose, it is often more acceptable to the patient to disperse powder in water and swallow it as a draught.

4. 3. Orally administered powders of soluble medicaments have a faster dissolution rate than tablets or capsules, as these must first disintegrate before the drug dissolves. Drug release from such powdered preparations will therefore generally be faster than from the corresponding tablet or capsule.

5. Disa dvantages of Powdered Products as Dosage Forms 1. Bulk powders (i.e. where doses are not pre - divided into individual aliquots) are far less convenient for the patient to carry than a small container of tablets or capsules, and are as inconvenient to sel f -administer as liquid preparations, such as mixtures. Modern packaging methods for divided preparations, such as heat-sealable laminated sachets mean that individual doses can be carried conveniently by the patient. 2. The masking of unpleasant tastes may be a problem with this type of preparation. 3. Bulk powders are not suitable for the administration of potent drugs with a low dose. This is because individual doses are extracted from the bulk with a 5 mL spoon. This method is subject to variation in spoon fill (e.g. ‘level’ or ‘heaped’ spoonful) and variation in the bulk density of different batches of the powde r . It is therefore not an accurate method of measurement. Divided preparations have been used for more potent drugs, but tablets and capsules have replaced them for this purpose.

6. 4. P owders are not a suitable form for the administration of drugs that are inactivated in, or cause damage to, the stomach; these should be presented as gastro-resistant tablets, for example.

7. CLASSIFICATION OF POWDERS Powders for Oral Administration Oral powders Oral powders are preparations consisting of solid, loose , dr y particle s o f varyin g degree s o f fin e particle size. They contain one or more active substances, wit h o r withou t e x cipient s and , i f necessar y , approved colouring matter and flavouring. They are generally administered in or with water or another suitable liquid, or they may also be swallowed directl y . They ar e presente d a s single-dos e o r multidos e preparations in suitable containers.

8. Oral Powders (Contd.) Each dose of a single-dose powder is enclosed in an individual container (e.g. a sachet or a vial). T raditionall y , single doses were wrapped in pape r . Thi s wa s unsatisfactor y fo r mos t products , particularl y if the ingredients were hygroscopic, volatile or deli- quescent . Modern packaging materials of foil and plastic laminates have largely replaced such paper wrappings; they offer superior protective qualities and are amenable to use on high-speed packing machines . Howeve r , pape r -wrappe d powder s continue to exist in some ove r -the-counter products.

9. Multidos e ora l powder s ar e packe d int o a suitable bulk containe r , such as a wide-mouthed glass ja r . They require the provision of a measuring device capabl e o f deliverin g th e quantit y prescribed . Because of the difficulty in precisely measuring single doses from this type of preparation, the constituents are usuall y relativel y nont o xi c medicament s wit h a large dose. R elatively few proprietary examples exist, althoug h man y dietary/foo d supplement s ar e packed in this wa y . I n th e manufactur e o f ora l powders , effor t i s made to ensure a suitable particle size is used with regard t o th e intende d use . A dditionall y , durin g manufacture, packaging, storage and distribution of oral powders, suitable means must be taken to ensure microbial qualit y . All powders and granules should be stored i n a dr y plac e t o preven t deterioratio n du e t o ingress of moisture. Even if hydrolytic decomposition of ingredients does not occu r , the particles will adhere and cake, producing an inelegant, often unusable product.

10. Effervescent powders Effervescent powders are presented as single-dose or multidose preparations and generall y , in addition to the drug, contain acid substances and carbonates or hydrogen carbonates which react rapidly and effervesc e whe n th e patien t add s th e powde r t o water to produce a draught. Citric acid plus sodium bica r - bonat e i s a commo n combinatio n tha t release s carbon di o xide. The drug is quickly dissolved or dispersed in the water before administration. It is preferred that effervescent powders are packed in individual dose units in airtight containers (laminated sachets are ideal ) . It is important to protect the powder from the ingress of moisture during manufacture and on subsequent storag e t o preven t th e reactio n occurrin g prematurel y .

11. Powders for other Routes of Administration Powders for inhalation The use of dr y -powder systems for pulmonary drug delivery is now extensive. This dosage form has developed into one of the most effective methods of delivering active ingredients to the lung for the treatmen t o f asthm a an d chroni c obstructiv e pulm o - nar y disease . It s popularit y i s reflecte d i n th e number of commercial preparations available in a number of sophisticate d an d increasingl y precis e deliver y devices.   Nasal powders Nasal powders are medicated powders intended for inhalatio n int o th e nasa l cavit y b y mean s o f a suitable device . Som e poten t drug s ar e presente d i n thi s way becaus e the y ar e rapidl y absorbe d whe n administered as a fine powder via the nose .

12. Powders for External Use Powders for cutaneous application (topical powders) P owders for cutaneous application are preparations consisting of solid, loose, dry particles of varying degree s o f fineness . The y contai n on e o r mor e active substances , wit h o r withou t e x cipient s and , i f nece s sar y , appropriate colouring matte r . P owders for cutaneous application are presented as single-dose powders or multidose powders. They shoul d b e fre e fro m grittines s (cause d b y th e presenc e of some large primary powder particles). P owders specifically intended for use on large open wounds or on severely injured skin must be sterile. Multidos e powder s fo r cutaneou s applicatio n ma y be dispensed in sifte r -top containers, in containers equipped with a mechanical spraying device or in pressurized containers.

13. In the manufacture of powders for cutaneous application, measures should be taken to ensure a suitable particle size is obtained (determined and controlled by sieving) with regard to the intended use. A dditionall y , suitable measures should be taken to ensure their microbial quality and if the label indicate s tha t th e preparatio n i s sterile , th e preparation must comply with a test for sterilit y . Steril e powder s use d i n cutaneou s applicatio n must be prepared with materials and methods designed to ensure sterility and to avoid the introduction of contaminants and the growth of microorganisms.

14. Dusting powders Dustin g powder s ar e powder s fo r cutaneou s applic a tio n whic h hav e a suitabl e fineness . A n exampl e i s T alc Dusting P owde r , which is a mix of 10% starch and 90 % Purifie d T alc , wher e th e particl e siz e i s controlled by size separation using, typicall y , a 250 µm sieve. Dusting powders contain ingredients used for therapeutic, prophylactic or lubricant purposes and are intended for external use. Only sterile dusting powders should be applied to open wounds.

15. Dusting powders for lubricant purposes or supe r ficial skin conditions need not be sterile but they shoul d b e fre e fro m pathogeni c organisms . A s minerals suc h a s tal c an d kaoli n ma y b e contaminate d a t source w i t h spo r e s o f or g an i sm s c a usi n g t et a nu s a n d g a ng r en e , thes e shoul d b e sterilize d befor e the y ar e incorporated into a product. T alc Dusting P owder is a sterile cutaneous powder in which the talc is sterilized before incorporation with the starch, or the final product is subject to a suitable terminal sterilization procedure. Dusting powders are normally dispensed in glass o r meta l container s wit h a perforate d lid . Th e powder must flow well from such a containe r , so that it can be dusted over the affected area. The active ingr edient s mus t therefor e b e dilute d wit h material s with reasonably good flow properties (e.g. purified talc or maize starch).

16. Hexachlorophene Dusting P owder contains an antibacterial agent, and T alc Dusting P owder is used a s a lubrican t t o preven t chafing . P roprietar y products are available, usually for the treatment of bacterial or fungal infections, e.g. Canesten® AF P owder (clotrimazole) is used as an antifungal agent.

17. Powder Preparations Requiring further Treatment at the Time of Dispensing Some preparations for oral use are prepared from powder s t o yiel d ora l solution s o r suspe n sion s usin g a suitabl e vehicle . Thi s ma y b e performed at the dispensing stage or by the patient prior to administration. The vehicle for any preparations for oral use is chosen with regard to the nature of the activ e substance(s ) an d suc h tha t i t provide s organ o lepti c characteristic s appropriat e t o th e intende d use of the preparation. Several categories of preparations may be distinguished: powders for oral solutions and suspensions; • powders for syrups; • powders for oral drops; and • powders for injection.

18. Powders for solution or suspension P owder s for the preparation of oral solutions or suspensions generally conform to the definitions in the normal pharmacopoeial standards for oral powders or granules as appropriate. They may contain e x cipients, in particular to facilitate dispersio n o r dissolutio n an d t o preven t caking . A fter dissolutio n o r suspension , th e resultin g produc t should comply with the requirements for oral solutions or oral suspensions, as appropriate. Th e labe l shoul d explai n th e metho d o f preparation of the solution or suspension from the powder or granules, and the conditions and the duration of storage after reconstitution.

19. Powders for syrups Syrups are aqueous preparations characterized by a sweet taste and a viscous consistenc y . They may contain sucrose at a concentration of at least 45%. The sweet taste can also be obtained by using other polyols or sweetening agents. Syrups usually contain aromatic or other flavouring agents. Al l o f th e necessar y ingredient s fo r th e syru p ma y be manufactured and stored in the dry powdered stat e an d the n reconstitute d (usuall y b y the addition of water alone) at the time of dispensing or administration . A fte r dissolution , th e resultin g syrup mus t compl y wit h th e norma l pharmacopoeia requir e ments for syrups.  

20. Antibioti c sy r ups . F o r patient s wh o hav e difficulty taking capsules and tablets (e.g. young children), a liquid preparation of a drug offers a suitable alternative. Unfortunatel y , many antibiotics are physically or chemically unstable when formulated as a solution or suspension. The method used to overcome this instability problem is to manufacture th e dr y ingredient s o f th e intende d liqui d preparation in a suitable container in the form of a powder or granules. When the product is dispensed, a given quantity of water is added to reconstitute the solution or suspension. This enables sufficient time for warehousing and distribution of the product and storage at the pharmacy without degradation. Once it is reconstituted, the patient must be warned of the short shelf life. A shelf life of 1–2 weeks for the reconstituted antibiotic syrup should not be a serious problem for the patient as the dosing would normally be completed by then. Am o xicillin Oral Suspension and Erythromycin Ethyl Succinate Oral Suspension are examples.

21. Powders for oral drops Oral drops are solutions, emulsions or suspensions that are administered in small volumes, such as in drops, by the means of a suitable device. P owders for the preparation of oral drops would have to confor m t o th e requirement s o f al l othe r ora l powders . They may contain e x cipients to facilitate dissolution or suspension in the prescribed liquid, or to prevent caking. A fte r dissolutio n o r suspension , the y compl y with th e specifi c pharmacopoeia l requirement s fo r pre - pr epared oral drops. If the dose is measured in drops, the label should also state the number of drops per millilitre or per gram of preparation.

22. Powders for injection Injection s o f medicament s tha t ar e unstabl e i n aqueous solution must be made immediately prior to administration. The ingredients are presented as sterile powder s i n ampoule s o r vials . Suf f icien t diluen t (e.g . sterile W ater for Injections) is added from a second containe r t o produc e th e require d dru g concentration, and the injection is used immediatel y . The powder may contain suitable e x cipients in addition to the drug (e.g. sufficient additive to produce an isotonic solution when the injection is reconstituted). P owder s fo r injectio n ar e mos t ofte n manufactured by a freeze-drying process . The label for powders for injection should state (1) the amount of active ingredient contained in the seale d containe r , (2 ) th e direction s fo r preparin g the injection or intravenous infusion from the powder and (3) that when dissolved or suspended, the preparation is intended for parenteral use.

23. REFERENCES Aulton’s Pharmaceutics: The Design and Manufacture of Medicines, 5 th Edition.