Multidose Powders

The preparation of the powder mixture is analogous to the preparation of single-dose powders (see Sect. 4.5), but the flow properties are less critical, because the powder mixture does not have to be distributed evenly over dose units. A diluent is generally not necessary, but in case it is required, lactose is often used. Bulk or multidose powders can be packaged in glass, plastic, metal or other containers that have a wide mouth to allow the handling of the powdermeasuring device. 

Sodium sulfate is an example of multidose powder, which is used as laxative in case of intoxication the patient should take several grams. To make this preparation more patient-friendly, the required quantity of Sodium sulfate decahydrate can be weighed into a dry bottle, which basically makes it a divided powder. Prior to use, the required amount of water is added to dissolve the powder. This may be drme in the pharmacy or elsewhere by the patient or the caregiver. An advantage of a powder over an oral solution is that the preparation has a l(Mig shelf life without the need for a preservative. 

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Newman SP, Moren F, Trofast E, Talaee N, Clarke SW. Deposition and clinical efficacy of terbutaline sulphate from Turbuhaler, a new multidose powder inhaler. Eur Respir J 1989 2(3) 247-252. 

Multidose powders have their containers opened several times while used, and thus, stability might become a problem. As a suggestion, when the chemical and physical stability are unknown, the maximum shelf life of the powders is limited to 6 months and the user informed towards a careful use of the container, particularly on having it open for the shortest possible time. 

Orally administered medicines require the pharmacist s advice on when (before, with or after the meal) and how (with a full glass of water, no milk, etc.) to take the medicine. When single-dose or multidose powders are dispensed, patients must be taught on the exact technique for measuring the dose to be administered and the proper mode of administration. Should the powder be mixed in a liquid What liquid and volume Can the powder be mixed with food (hot or cold) How long it can be kept after mixing ... 

Powders for inhalation are not defined other than that they are presented as single-dose or multidose powders and that the active substances may be combined with a suitable carrier to facilitate their use. If the powder is for a singledose (pre-metered) inhaler, the device is loaded with powders pre-dispensed in capsules or other suitable pharmaceutical forms. For inhalers using a powder reservoir, individual doses are isolated from the bulk with a metering mechanism within the inhaler. 

Mixing of solids takes place in the pharmacy in the preparation of capsules, single-dose powders and multidose powders. But also in the preparation of suppositories and dermal preparations solids may first be mixed together before they are combined with the base. A common reason for this is that mixing solids may give an opportunity to ... 

In ampules or vials that contain powder or crystals, to which a liquid (called a diluent) must be added before the drug can be removed from die vial and administered. Vials may be single dose or multidose vials. 

The metering of dry powder inhalers is closely linked to the device itself and may be divided into three common systems capsules, multidosing blister packs, and reservoir systems. The consideration that goes into these metering systems include convenience to the patients, stability on storage, compatibility with product, and ease of filling. 

Reservoir Multidose and dose titration easy Powder not generally well protected... 

Dosage form /ntron A is supplied as a sterile lyophiUzed powder for injection and a solution for injection. Intron A solution for injection in multidose pens contains a prehUed, multidose cartridge for subcutaneous administration. 

Figure 2 Schematic example of a multidose dry powder inhaler.

The Easyhaler (by Orion Pharma, Finland) and the Clickhaler (by Innovata pic, United Kingdom) are available at present in some European markets. Unlike the DPIs described earlier, these two reservoir-type inhalers meter the dose when the patient presses the top of the device similar to actuation of a pressurized metered-dose inhaler. Both devices contain a dose indicator, which is standard for reservoir multidose DPIs. Recently, Innovata presented the Twinhaler for asthma combination therapy, a new development based on the Clickhaler. This device does not require the combined drugs to be formulated in one powder blend but delivers two powder formulations from two reservoirs into one airflow path. 

FIGURE 4 (a) Optinose multidose liquid device and (b) Optinose multiuse powder device. (Reproduced with permission of Per Gisle Djupesland by personal communication.)... 

Reservoir Multidose and dose titration easy to implement Convenient—no separate unit-dose blisters to worry about Powder not generally well protected after reservoir is opened physical and/or chemical characteristics may deteriorate with time Biological contamination may be an issue Metering of the dose is carried out by the device, which increases the device complexity metering often is not adequately controlled because the physical characteristics of the powder are often unknown at the time of dosing... 

Formoterol is a long-acting selective beta2-adrenoceptor agonist that is more potent than salmeterol (1) and has a similar duration of action (12 hours) but a rapid onset of effect similar to that of salbutamol. It is available as a multidose, pressurized aerosol and as a dry powder inhaler, delivering 0.006 or 0.012 mg per dose. The usual dose is 0.012 mg bd. 

Formoterol 12 and 24 micrograms, delivered from either a multidose pressurized aerosol or a dry powder inhaler, did not affect heart rate. However, at doses of 48 and 96 micrograms the heart rate rose significantly after the dry powder formulation. Tremor was significantly higher after the 48 micrograms dose of dry powder compared with the multidose pressurized aerosol. The two formulations were equipotent in producing bronchodilatation (SEDA-21, 184). 

Salmeterol is a selective beta2-adrenoceptor agonist that is more potent and has a significantly longer duration of action than salbutamol (SEDA-21, 184). It is used as a supplement to inhaled glucocorticoids for sustained bronchodUatation. It has a much slower onset of effect than salbutamol and is not effective in acute attacks of asthma. It is available as a multidose-pressurized aerosol 0.025 mg/puff, and as a dry powder, Diskhaler or Accuhaler 0.05 mg per dose. The adverse effects profile of salmeterol is the same as that of salbutamol and other betaz-agonists (SEDA-21, 185). 

Dry powder inhalers These are inhalers that typically fall into two general types of commercially available systems single-dose and multidose systems. The multidose systems have been finding increased use in recent years and are generally either passive devices, where the patient provides the energy to disperse the drug powder in a stream of inspired air, or active devices, in which the energy comes from the device. 

The development of multidose DPIs was pioneered by A. B. Draco (now a division of AstraZeneca) with their Turbuhaler [53]. This device is truly a metered-dose powder delivery system. The drug is contained within a storage reservoir and can be dispensed into the dosing chamber by a simple back-and-forth twisting action on the base of the unit (Fig. 7). The device is capable of working at moderate flowrates and also delivers carrier-free particles [54]. However, one of the drawbacks of the Turbuhaler has been the fact that it has... 

Figure 7 Components of the Turbuhaler, a multidose dry powder inhaler. (1) mouthpiece with insert, (2) bypass air inlet, (3) inhalation channel, (4) air inlet, (5) desiccant store, (6) window for dose indicator, (7) dose indicator, (8) storage unit for drug compound, (9) dosing unit, (10) operating unit, (11) turning grip.

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