Orodispersible drug delivery systems

Transcription

1 Orodispersible drug delivery systems

2 Orodispersible drug delivery systems Disintegrate and/or dissolve rapidly in the saliva without the need for water. Tablets Films Fast-dissolving tablets are designed to dissolve in saliva remarkably fast, within a few seconds Fast- disintegrating contain agents to enhance the rate of tablet disintegration in the oral cavity

3 European Pharmacopoeia adopted the term Orodispersible Tablet as a tablet that to be placed in oral cavity where it disperses rapidly before swallowing. There are multiple fast-dissolving OTC and Rx products on the market worldwide There is increases in the number of new chemical entities under development using a fast-dissolving drug delivery technology. Anti-ulcer (e.g. Omeprazole), antiasthamatics (salbutamol sulphate), antitussives, expectorants, antihistaminics, NSAID S (e.g. paracetamol, meloxicam, valdecoxib).

4 Advantages of orodispersible dosage forms Ease of administration for patients who are mentally ill, disabled and uncooperative. Requires no water Self administration. Overcomes unacceptable taste of the drugs and could provide a pleasant mouth feel. Allows high drug loading. Provide advantages of liquid medication in the form of solid preparation. Adaptable to existing processing and packaging machinery. Increased bioavailability (pre-gastric absorption ).

5 Advantages of orodispersible dosage forms While the claimed increase in bioavailability is disputable, it is clear that the major advantage of these formulations is convenience

6 Approaches for orodispersible Tablets The fast-dissolving property of the tablet is attributable to a quick ingress of water into the tablet matrix resulting in its rapid disintegration. The basic approaches to developing orodispersible dosage forms tablets are: Maximizing the porous structure of the tablet matrix Incorporating the appropriate disintegrating agent Using highly water-soluble excipients

7 Conventional Techniques Used in the Preparation of Orodispersible Tablets Lyophilization Tablet Molding Direct compression Spray drying Sublimation Mass extrusion

8 Freeze drying or Lyophilization A process in which water is sublimated from the product after freezing.

9 Freeze drying or Lyophilization Scanning electron images of orodispersible tablets prepared by lyophilization

10 Freeze drying or Lyophilization Advantages: Tablets are highly porous, with a very high specific surface area, which dissolve rapidly and show improved absorption and bioavailability. Disadvantages: Tablets are fragile with low mechanical strength, which make them difficult to handle and require special packaging. They are hygroscopic and exhibit poor stability on storage under stressed conditions.

11 Molding moistening the powder blend with a suitable solvent followed by putting into mold plates. The solvent is then removed.

12 Molding Compression molding Air drying of a hydroalcoholic solvent No-vacuum lyophilization Evaporate a frozen mixture containing a gum at standard pressure Heat molding Drying solidified agar at C under vacuum Moulded tablets typically do not possess great mechanical strength. Erosion and breakage of the moulded tablet often occur during handling and opening of blister packs.

13 Spray drying The formulations contained: Gelatin as a support agent for the matrix Mannitol as a bulking agent Na starch glycolate or crosscarmellose as a disintegrant. The formulation was spray dried to yield a porous free flowing powder. Tablets manufactured from this powder disintegrated in less than 20 s in an aqueous medium.

14 Spray drying Solvent evaporation Drug solution or slurry is sprayed Steam of hot gas Drug powder

15 Sublimation Conventional compressed tablets containing highly water-soluble ingredients and volatile ingredients. The volatile material is removed by sublimation, leaving behind a porous matrix.

16 Sublimation

17 Sublimation Inert solid ingredients that displayed high volatility : ammonium bicarbonate benzoic acid hexamethonium tetramine phthalic anhydride Urethane water ammonium carbonate Camphor Naphthalene Urea cyclohexane & benzene

18 Direct compression Advantages: Easy Conventional equipment Commonly available excipients Limited number of processing steps High doses can be accommodated

19 Direct compression Disintegrants Sugar-based excipients dextrose, fructose, isomalt, maltitok, maltose, mannitol, sorbitol, starch hydrolyse, polydextrose, and xylitol Superdisintegrants Microcrystalline cellulose crospovidone croscarmellose Na Effervescent disintegrating agents

20 Mass extrusion This technology involves softening the active blend using the solvent mixture of water soluble polyethylene glycol, using methanol and expulsion of softened mass through the extruder or syringe to get a cylinder of the product into even segments using heated blade to form tablets.

21 Mass extrusion

22 Patented Technologies for orodispersible Tablets Some patented technologies are available. Each technology has a different mechanism, and each fastdissolving/disintegrating dosage form varies regarding the following: -Mechanical strength of final product; -Drug and dosage form stability; -Mouth feel; -Taste; -Rate of dissolution of drug formulation in saliva; -Swallowability; -Rate of absorption from the saliva solution; and -Overall bioavailability.

23 Zydis Technology The first marketed fast dissolving tablet. Produced by lyophilizing Usually consisting of gelatin

24 Zydis Technology Tablet properties: Dissolves in the mouth within seconds. Very lightweigh, fragile, and must be dispensed in a special blister pack. Self-preserving because the final water concentration in the freeze-dried product is too low to allow for microbial growth. The drug amount is less than 60 mg for soluble drugs. Particle size of insoluble drugs between mm to prevent sedimentation during processing. Has poor stability at higher temperatures and humidities.

25 Orasolv Technology A fast-disintegrating tablet with drug microparticles and effervescent disintegrant. Prepared by conventional blenders and tablet equipment using Less force of compaction. OraSolv products disintegrate rapidly in the mouth without chewing. Drug microparticles are released and swallowed as a slurry or suspension. Complete dissolution and systemic absorption occurs in the GI tract. Typically, the pharmacokinetics are matched to the reference product.

26 Orasolv Technology Tablet properties: Their disintegration time is less than 30s. The OraSolv formulations are not very hygroscopic. This technology involves taste masking of active drug. Tablets are soft and fragile They require a special handling and packaging system.

27 Durasolv Technology Produced in a fashion similar to OraSolv with much higher mechanical strength. Tablets are durable and can be packaged in traditional blister packaging, pouches or vials. This technology is best suited for formulations including relatively small doses of active compound.

28 Flash Dose Technology This technology utilizes a unique spinning mechanism (flash heat processing) Shearform technology A floss-like crystalline structure to incorporate the active drug and be compressed into a tablet It has a very high surface area for dissolution. It disperses and dissolves quickly once placed onto the tongue. Ceform technology Small spheres of saccharides to carry the drug The formed microspheres serves as a method of taste masking.

29 Flash Dose Technology Tablet properties: The tablet can accommodate only up to 600 mg drug. Tablets produced are highly friable, soft and moisture sensitive. Therefore specialized packing is required.

30 Wowtab Technology With Out Water This process uses a combination of two different types of saccharides combined to obtain a tablet formulation with adequate hardness and fast dissolution rate. low mouldability saccharides (rapid dissolution) high mouldability saccharide (good binding property).

31 Wowtab Technology With Out Water Tablet properties: The Wowtab product are stable Suitable for both conventional bottle and blister packaging. Offer superior mouth feel Tablets dissolves quickly in 15 seconds

32 Flashtab Technology Rapidly disintegrating tablet consisting of an active ingredient in the form of microcystals coacervation extrusionspheronization microencapsulation pan coating The microcrystals of the active ingredient are added to the granulated mixture of excipients prepared by wet or dry granulation, and compressed into tablets.

33 Flashtab Technology Tablet properties: Utilize the conventional tabletting technology Tablets have good mechanical strength Disintegration time less than 1 min. Taste-masking

34 Oraquick Technology Fast-dissolving/disintegrating tablet formulation utilizes a patented taste masking microsphere technology, known as MicroMask technology.

35 Tablet properties: Oraquick Technology The process does not utilize solvents of any kind, this leads to faster and more efficient production. Appropriate for heat-sensitive drugs. Good taste-masking. Tablets can be compressed to achieve significant mechanical strength without disrupting taste masking. Has quick dissolution in a matter of seconds

36 Nanocrystal Technology NanoCrystal colloidal dispersions of drug substance are combined with water-soluble ingredients, filled into blisters and lyophilized. NanoCrystal particles are small particles of drug substance, typically less than 1000 nm in diameter, which are produced by milling the drug substance using a proprietary wet milling technique

37 Nanocrystal Technology Product properties: The wafers dissolve in very small quantities of water in seconds. Attractive for highly potent drugs because manufacturing losses are negligible For hazardous materials because it avoids manufacturing operations (e.g., granulation, blending, and tableting) that generate large quantities of aerosolized powder and present much higher risk of exposure.

38 Evaluation tests for orodispersible tablets? In-vitro In-vivo

39 Fast-dissolving films Fast-dissolving films are gaining interest as an alternative to fast-dissolving tablets to definitely eliminate patients fear of chocking and overcome patent impediments. They dissolve in saliva requiring no water to take. Examples for film-forming polymers: modified starches (maltodextrin), gums (xanthan & guar gum), cellulose ethers, alginates, polyvinylalcohols, polyvinylpyrrolidones or blends

40 Fast-dissolving films Plasticizers Are important factors affecting mechanical properties of films (such as tensile strength and elongation) Variation in their concentration may affect these properties. The commonly used plasticizers are glycerol, dibutylpthallate and polyethylene glycols

41 Fast-dissolving films Manufacturing Methods 1) Solvent casting. 2) Semisolid casting. 3) Hot melt extrusion. 4) Solid dispersion extrusion. 5) Rolling.

42 Solvent casting method water soluble polymers are dissolved in water and the drug along with other additives is dissolved in suitable solvent then both the solutions are mixed, stirred and finally casted in to the Petri plate, and dried. Aqueous solution Solvent

43 Fast-dissolving films Evaluation of fast-dissolving films Film thickness Film flexibility Tensile properties Stickiness determination Drug content Disintegration test Measurement of the disintegration in the oral cavity In vitro dissolution test

44 Fast-dissolving films TECHNOLOGIES 1) SOLULEAVES technology 2) WAFERTAB 3) FOAMBURST 4) XGEL film 5) Quick Dis Technology

45 Quick Dis Technology A thin, flexible and quick-dissolving film Film properties: Provided in various packaging configurations, ranging from unitdose pouches to multiple-dose blister packages. The typical disintegration time is only 5 to 10 seconds. The dissolving time (at which not less than 80% of the tested film is dissolved in aqueous media) is around 30 seconds The typical release profile of an active ingredient exhibited by a Quick-Dis drug delivery system is 50% released within 30 seconds and 95% within 1 minute.