Drug Delivery to the Oral Cavity

?
  • Created by: LBCW0502
  • Created on: 13-02-19 11:39
What are the three types of oral route of administration? (1)
Buccal (apply to lining of cheek to enter systemic circulation following absorption). Sublingual (apply to membranes either floor or mouth or underside of tongue and enter systemic circulation following absorption)
1 of 69
What are the three types of oral route of administration? (2)
Local (apply directly to site of action, buccal/sublingual, to treat local conditions e.g. ulcers). Routes have rich blood supply/highly vascularised
2 of 69
Why is the oral route of administration used? (1)
Sites for delivery differ in both structure an composition as well as their degree of permeability and also vary in their availability to retain a delivery device for desired length of time
3 of 69
Why is the oral route of administration used? (2)
Different retention times e.g. oral cavity produces secretions to break down tablet but tablet can be made to stick to cheek wall (reduce disintegration). First potential site for absorption for orally administered drugs
4 of 69
Why is the oral route of administration used? (3)
Drugs avoid GI enzymes and first pass metabolism
5 of 69
What are the two regions in the oral cavity which are suitable for oral administration?
Outer oral vestibule which is bounded by the cheeks and lips (true buccal cavity). Interior oral vestibule which is behind the teeth (oral cavity)
6 of 69
Describe features of the oral epithelium structure (1)
Consists of stratified squamous epithelium. Mostly keratinised like skin but degree varies with region. Hard palate, gingiva and tongue are keratinised whilst floor of mouth, soft palate, lips and cheek are not
7 of 69
Describe features of the oral epithelium structure (2)
100-200 micrometres epithelium thickness on underside of tongue and on floor of mouth. 500-800 micrometres in buccal cavity
8 of 69
Describe features of the oral epithelium structure (3)
Epithelium inside mouth is secretory – mucus. Mucous epithelium – eye, nose, lung, gut. More vascularisation in buccal cavity and more epithelium
9 of 69
Describe features of the oral epithelium structure (4)
Sebaceous glands (60-75% in adults). Salivary glands (parotid, sublingual, submandibular). Relative to skin there is a greater density of blood vessels/lymphatic vessels are also present. Protective during chewing (mastication)
10 of 69
Describe features of the oral epithelium structure (5)
Cheeks are elastic to allow distension. Responds to pain/touch/temperature/taste (unique). Swallowing, gagging and retching. Thermoregulation e.g. panting in dogs
11 of 69
Describe features of secretion of saliva (1)
Parotid/submandibular (submaxillary)/sublingual glands connected via long ducts. Submandibular/parotid glands produce a watery fluid whereas sublingual/buccal glands produce saliva
12 of 69
Describe features of secretion of saliva (2)
1 L/day, resting level 0.05 mL/min. Rises to 7 mL/min upon stimulation. Viscous/colourless/odourless/opalescent/hypotonic. Specific gravity of 1.003. pH 6.2 and 7.4 rises with flow rate. Bacteria reduce pH to 3/4
13 of 69
Which enzymes are released in saliva? (1)
Alpha-amylase (ptyalin) which begins hydrolysis of polysaccharides. Optimum pH for activity is 6.9 but it is active over a range of pHs from 4-11 (works until it encounters low pH of stomach)
14 of 69
Which enzymes are released in saliva? (2)
Hydrophobic lipase capable of hydrolysing triglycerides (even in the stomach). Lysozyme, thiocyanate ions and antibodies present for antibacterial action. Mucus, enzymes and inorganic ions
15 of 69
What does xerostomia mean?
Dry mouth, adverse effect for many drugs. Balance of secretion of saliva is affected by drugs
16 of 69
What are the factors affecting dosage form for the sublingual route?
Relatively permeable, rapid/appreciable absorption. Unsuitable for retentive systems. Ideal for LMW lipophilic drugs for rapid onset of action/no tight junctions. Sprays, fast dissolving tablets
17 of 69
What are the factors affecting dosage form for the buccal route?
Relatively less permeable. Not rapid onset of absorption. Highly suitable for retentive systems. Ideal for sustained release. Adhesive tablets or patches. Doesn't affect eating or drinking
18 of 69
Describe the absorption of drugs (1)
Oral epithelium is a lipid barrier, intracellular space containing lipidic materials from membrane coating granules. Paracellular routes (desmosomes) transcellular passive diffusion or active transport (carrier mediated) endocytosis
19 of 69
Describe the absorption of drugs (2)
Bioavailability can be as high as IV injection. Delivery system can be removed during therapy. Absorption is affected by physicochemical properties of the drug, structure, physiology, composition of oral mucosa and formulation of delivery system
20 of 69
Describe the absorption of drugs (3)
Amount of drug permeating depends on concentration of drug on mucosa, log P, degree of contact between drug and membrane and contact time. Absorption is passive with suitable log P/well absorbed/sublingual
21 of 69
Describe the absorption of drugs (4)
Dosage form must remain in place during absorption, drug should be tasteless, sublingual route not useful for long term absorption (dilution by saliva). Rate of dissolution can be position dependent due to variations in flow/water content of saliva
22 of 69
Describe the absorption of drugs (5)
Originally used to avoid first pass metabolism but more recent studies show fast dissolving dosage forms produce a rapid response
23 of 69
Why is there a higher plasma isosorbide dinitrate concentration for sublingual compared to buccal?
Sublingual - not enough contact time (*LC)
24 of 69
Describe features of sublingual nitroglycerin (1)
Relieves symptoms within 2 mins. Sublingual tablets consist of lactose mannitol sucrose (fast dissolution). Disintegrates, taste-masking, heating/cooling effect impacts on taste. Stability issues (heat/light/moisture)
25 of 69
Describe features of sublingual nitroglycerin (2)
Lipid aerosol formulation (spray) more stable than tablets. Sublingual route avoids first pass metabolism (rapid absorption, eliminates symptoms rapidly)
26 of 69
What are the two types of oral mucosal drug delivery systems?
Mobile/non-attached or immobilised. Drug delivery system must ensure that the drug is released in a controlled manner and that a sufficiently high drug concentration is delivered to the mucosal surface
27 of 69
Give examples of non-attached drug delivery systems
Fast dissolving tablet dosage forms and chewing gums. E.g. gum, lozenges, fast dissolving tablet dosage forms (introduced to buccal cavity, high concentration, covers whole area, no binders/disintegrants
28 of 69
Describe features of fast dissolving dosage forms (1)
Creates high concentration of drug in oral cavity covering a large SA. Tablets similar to conventional ones without disintegrants. Lozenges also do not contain disintegrants and often contain sucrose, lactose and gelatin to provide a smooth feel
29 of 69
Describe features of fast dissolving dosage forms (2)
Freeze dried forms often dissolve within 15 seconds in vitro but there is no evidence that the drugs will be absorbed during this time
30 of 69
Which factors tend to decrease the effectiveness of tablets? (1)
Residence time (very short due to removal of from oral cavity following swallowing). High inter/intra individual variability (bioavailability, expected due to modifications of delivery rates)
31 of 69
Which factors tend to decrease the effectiveness of tablets? (2)
(by physiological factors such as variable salivary secretion or tongue movement). Released drug is not protected from environment of oral cavity e.g. enzymes
32 of 69
Describe features of Zydis (1)
Fast dissolving dosage form. Freeze-dried which melts when it is placed in the mouth. Benefits - used in patients with swallowing difficulties/no access to water, reduction of non-compliance
33 of 69
Describe features of Zydis (2)
Improvement in blood levels due to increased rate of absorption by eliminating first pass effect and allowing absorption from buccal cavity, pharynx and oesophagus
34 of 69
Give other examples of fast dissolving formulations
Benzocaine (Orafilm), Zyprexa Zydis (olanzapine - antipsychotic, improve adherence), Zydis product - Feldene Melt (piroxicam)
35 of 69
Describe features of the formulation of Zydis (1)
Disperses instantaneously in the mouth due to their high porosity and low mass. Allows rapid ingress of saliva so that soluble components of matrix rapidly dissolve releasing drug as solution or suspension on tongue
36 of 69
Describe features of the formulation of Zydis (2)
API suspended/dissolved in gelatin/mannitol, poured into mould, frozen, freeze-dried. Sweetening (aspartame), colouring, flavouring agents added. Dosage form holds 450 mg of drug, 10-20 mm in diameter. Contains 3-8% water
37 of 69
Describe features of the formulation of Zydis (3)
Particle size must be 50 micrometres or less to prevent sedimentation (can affect freeze drying)
38 of 69
Describe features of freeze drying
A dehydration process. Freeze material and reduce pressure (place in vacuum) and provide enough head to allow the frozen water in the material to sublime form solid to gas phase. Relates to phase diagram. E.g. naloxone
39 of 69
Describe features of the phase diagram
Boundary between gas a liquid runs from triple point to critical point. Freeze drying bring system around the triple point, avoiding direct liquid-gas transition seen in ordinary drying. Porous powder formed
40 of 69
What are the ideal properties of a disintegrating tablet?
Solid state (amorphous), short disintegration time, drug content, size/cover typical fingerprint area, physical stability/size/disintegration time, chemical stability/drug content. Marketed oral system products (e.g.)
41 of 69
Describe features of chewing gum formulations (1)
Sublingual mucosa is the main target (drug released in saliva, spreading may cause absorption to occur across other mucosa of oral cavity)
42 of 69
Describe features of chewing gum formulations (2)
Formulations consist of base of cellulose or acrylic polymer with sugars. Drug release generally not rapid but not as immediate as fast dissolving tablets (ascorbic acid, release after 5 mins, not increase after 30 mins)
43 of 69
Describe features of chewing gum formulations (3)
Release period can be extended by associating the drug with an ion exchange resin
44 of 69
Describe features of an ion exchange resin
Charged beads (can be polymer, or part of chewing gum), can associated drugs via electrostatic interactions (acid/base), bead carries drug molecules in ionic state, dissociates depending on pH of saliva (prolongs release of drug formulation)
45 of 69
What are the problems associated with the dosage form? (1)
Drug released into saliva/disappears rapidly from oral cavity due to involuntary swallowing. Concentration of drug in oral cavity decreased by continuous salivary dilution. Drug not protected from physiological environment
46 of 69
What are the problems associated with the dosage form? (2)
Drug release strongly influenced by the way the patient sucks/chews formulation. Administration restricted to short periods/presence of delivery system in oral cavity is a handicap in drinking/eating/speaking (not for drug release over long periods)
47 of 69
Nitroglycerin and prochlorperazine (antipsychotic-antiemetic) are in which types of formulations?
Solutions and sprays e.g. nitronal spray, VitaMist etc.
48 of 69
What are the advantages of immobilised drug delivery systems? (1)
Intimate contact developed between drug and mucosa. High drug concentration maintained at absorptive surface for prolonged period of time. Dosage form immobilised on buccal, labial, sublingual or gingival mucosa
49 of 69
What are the advantages of immobilised drug delivery systems? (2)
System itself can protect the drug from environmental degradation
50 of 69
Design must impart which two specific properties to the delivery system?
Immobilisation and controlled release. Only achieved by use of polymers. Bioadhesion/mucoadhesion by use of polymers can achieve immobilisation of dosage form (concept applied to sustained release, semi-dosage, films, patches, powders, microspheres)
51 of 69
Which polymer is responsible for controlled release?
HPMC. Difficult to choose polymer adhesive – need to consider safety/study extensively
52 of 69
What are the advantages of oral transmucosal drug delivery?
Relatively large SA (100 cm^2). Accessibility. Low metabolic activity. Variety of dosage forms. Solutions, emulsions, suspensions, sublingual, sprays, tablets, patches
53 of 69
What are the disadvantages of oral transmucosal drug delivery?
Mucus and salivary clearance. Poor permeability. Low potential for systemic administration. Inconvenience - advantages lost if swallowed
54 of 69
Give two examples of buccal dosage forms
Buccastem (prochlorperazine, antiemetic, in a polysaccharide base). Suscard buccal (long acting nitroglycerin, cellulose). - buccal sustained release of furbiprofen (NSAID)
55 of 69
Give examples of adhesive tablets (1)
Monolithic (easy to manufacture, hold large amounts, coating produces unidirectional drug release). Bilayered (unidirectional release, drug in adhesive layer protected by inert layer facing into oral cavity)
56 of 69
Give examples of adhesive tablets (2)
(drug incorporated into upper non-adhesive layer so drug is released into oral cavity). Multilayered (allow geometrical arrangements, cellulosic/acrylic polymers offer immediate high adhesion for prolonged periods of time, even in high drug content)
57 of 69
What are the limitations of adhesive tablets?
Small contact SA with mucosa, lack of flexibility, high drug release rates cannot be obtained, extent/frequency of contact may cause irritation
58 of 69
Which polymers can be used for flexible, adhesive films and laminated adhesive patches?
Cellulose derivatives e.g. celluloses - MC, CMC, HEC, natural gums - guar gum, karaya gum, agarose, polyacrylates - poly(acrylic acid), poly(methacrylic acid). Polymers exhibit mucoadhesive properties in presence of water, polyacrylic-based hydrogels
59 of 69
Describe features of buccal delivery patches
Multidirectional release (drug loss due to dissolution in the saliva). Unidirectional release (impermeable backing, small area for drug absorption)
60 of 69
What are the mechanisms and types of patches?
Matrix or drug adhesive systems. Reservoir system. Drug passes through membrane via diffusion before reaching mucosa, reservoir system would not disintegrate/disperse but emptied over period of time
61 of 69
Describe features of flexible, adhesive films and laminated adhesive patches (1)
Adhesive patches can be designed for either unidirectional or bidirectional release. Adhesive part can be used as drug carrier or as simple adhesive for retention of drug-loaded non-adhesive layer on mucosa. Peripheral adhesive ring is feasible
62 of 69
Describe features of flexible, adhesive films and laminated adhesive patches (2)
Use of impermeable backing layer will maximise drug concentration gradient and prolong adhesion due to system being protected from saliva. Systems 1-3 cm in diameter with area up to 10 cm^2 depending on site of administration
63 of 69
Describe features of flexible, adhesive films and laminated adhesive patches (3)
PAA based patches used for delivery of opioid analgesics (bioavailability increased from 5% to 35-50%) e.g. Uluru Oradisc - benzocaine for treatment of oral pain
64 of 69
Local delivery is used to treat which conditions?
Periodontal disease, gingivitis, oral candidiasis, chronic lesions, topical infections
65 of 69
What are the traditional methods of local delivery? (1)
Chewing gums, mouthwashes, ointments, gels - but they have short residence times (fail to maintain therapeutic concentrations long enough to affect bacterial population, also swallowing leads to losing drug
66 of 69
What are the traditional methods of local delivery? (2)
Patient compliance may be poor due to the need for frequent administration
67 of 69
Give examples of formulations with prolonged action (1)
Orabase (ointment made from pectin, gelatin, CMC in PEG, mineral oil base, mucoadhesive retained up to 2.5 hrs depending on site). Slow release tablets (based on PAA, PEG, CMC to deliver fluoride, levels maintained up to 8 hrs)
68 of 69
Give examples of formulations with prolonged action (2)
Gels (contains metronidazole for treatment of local fungal infections although needs to be applied several times a day). Mucosal oral therapeutic system (mots) - osmotic system containing nystatin
69 of 69

Other cards in this set

Card 2

Front

What are the three types of oral route of administration? (2)

Back

Local (apply directly to site of action, buccal/sublingual, to treat local conditions e.g. ulcers). Routes have rich blood supply/highly vascularised

Card 3

Front

Why is the oral route of administration used? (1)

Back

Preview of the front of card 3

Card 4

Front

Why is the oral route of administration used? (2)

Back

Preview of the front of card 4

Card 5

Front

Why is the oral route of administration used? (3)

Back

Preview of the front of card 5
View more cards

Comments

No comments have yet been made

Similar Pharmacy resources:

See all Pharmacy resources »See all Drug Delivery to the Oral Cavity resources »