Dosage Forms Exam 3 Sublingual Buccal

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The oral cavity is a complex but promising area for drug delivery.
Buccal
Sublingual

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Buccal- lining of cheek (usually between the cheek and gums)
Sublingual- Ventral surface of tounge and floor of mouth

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Two general purposes for administering drugs to the oral cavity:

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1. To achieve a systemic effect
2. To achieve a local effect

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Structure and properties are intermediate between the intestinal mucosa and epidermis

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Coated with mucus but a squamous epithelium.

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Epithelium

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The principle barrier for drug absorption
Highly vascularized-good for systemic delivery

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Variations in the oral mucosae

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Keratinization-helps to form a tough barrier
Buccal and sublingual membranes are not keratinized

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Thickness
Buccal > sublingual

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Buccal epithelium is 2-8x as thick

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Permeability

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Sublingual > buccal

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Saliva

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pH about 7

is critical for drug delivery- it can dissolve

Anatomical variations in amounts-regional differences e.g. a pool of saliva under the toung

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Advantages of Sublingual/Buccal Delivery

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1. Avoidance of GI acid degradation, GI enzymatic degradation, and the hepatic first pass effect
2. Can achieve rapid onset of action and high blood levels (for some drugs)
3. Can also be used for prolonged action

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Avoidance of GI acid degradation, GI enzymatic degradation, and the hepatic first pass effect

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No hepatic first pass, drainage is to jugular vein

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Can achieve rapid onset of action and high blood levels (for some drugs)

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Rapid action
SL NTG 1-3 min

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Can also be used for prolonged action

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can be several hours for buccal

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Disadvantages of Sublingual/Buccal Delivery

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Relatively low permeability for most drugs
e.g., Small, lipophilic drugs are best absorbed
2. The drug can be washed away
3. Sometimes unpredictable bioavailability

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Relatively low permeability for most drugs

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Because of skin like barrier properties

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The drug can be washed away

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by saliva, eating, drinking

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Sometimes unpredictable bioavailability

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due to mucosal variations

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Sublingual products

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designed for rapid drug release over a short period of time-drug dissolves in sublingual pool of saliva

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Buccal

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generally designed for slower drug release* over a sustained period of time-has lower permeability, relatively easy to keep dosage form in place

some buccal products work faster (See fentanyl below)

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The drug and excipients should be bland and non-irritating

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so as to not stimulate saliva flow

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Sublingual administration
- Tablets

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designed to disintegrate rapidly and leave little residue

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Compressed tablets

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usually lightly compressed-to facilitate disintegration

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Nitroglycerin

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Nitrostat (Pfizer),
Besides serving as a diluent, lactose has another purpose for SL NTG tablets-reduces explosive risk and help stabalize by reducing volatility

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Isosorbide dinitrate

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Sorbitrate (ICI)

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Lyophilized tablets
”Fast-dissolving tablets”

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Example: Asenapine (Saphris (Schering-Plough))-peak plasma concentrations between .5-1.5 hrs, reduced if water drank within 10 min
– also available in a black cherry flavor version

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Molded tablets (Tablet triturates)

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Prepared by forcing a moistened blend of drug and excipients into a mold, followed by forcing the wet
mass out of the mold and allowing to dry-tend to be softer than compressed tablets
Tablet molds are also available for extemporaneous compounding

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Usage of sublingual NTG tablets:

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Must be dispensed in the original glass container.-interacts and passes through plastic

Advise to keep tablet in the original container.

Advise to close cap tightly after use.- volatile may slowly evaporate

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Spray

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nitroglycerin - Nitrolingual Spray (Rorer)-sprayed on or under tounge, do not have to fumble with tablets

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Film

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Drug is uniformly mixed with a fast-dissolving polymer (e.g., cellulose-based), plus a plasticizer,
flavors, colorants, etc.

The technology is also used for some products intended for GI absorption

One intended for sublingual absorption: Suboxone (buprenorphine and naloxone) Sublingual Film

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Buccal administration

Chewing gum

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nicotine
1.high hepatic first pass
2. good buccal absorption

Nicotine bound to a cation exchange resin-nicotine exchanged with saliva cat ions

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nicotine continued

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Formulated with buffer to raise the pH to 8.5- basic PH increases the nonionized form

The systemic bioavailability depends on the time the saliva is held in the mouth- if swallowed nicotine hepatically metabolized

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Lozenges

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Hard tablets, typically prepared like hard candy- dissolve slowly in the mouth

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Example of Lozenge

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nicotine polacrilex "Commit"
Similar to Nicorette, the nicotine is bound to a cation exchange resin- nicotine released by cation exchange as lozenge dissolves

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Lollipops

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Essentially a lozenge-on-a-stick

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Example of Lollipop

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fentanyl citrate lollipop "Actiq"-

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Atiq

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placed between cheek and gums, then sucked for about 15min

rapid absorption followed by prolonged absorption- rapid from absorption in the mouth

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Atiq Continued

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nice features are that the lollipop is unlikely to be swallowed and can be easily removed- if side effects

must be disposed of properly- keep away from children

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Mucoadhesive Tablets

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Goal- to keep in place

Designed to slowly disintegrate/dissolve

Contain mucoadhesive excipients

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mucoadhesive excipients

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cellulose derivatives

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Example of Mucoadhesive Tablets

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Striant (testosterone buccal system)
1. Testosterone- high hepatic first pass
2. stays until removed around 12hrs

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Orally Disintegrating Tablets (for Buccal Drug Delivery)

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Not all orally disintegrating tablets are meant for GI absorption

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Examples of Orally Disintegrating Tablets for buccal absorption

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Zelapar (selegiline hydrochloride) Orally Disintegrating Tablet

Fentora (fentanyl citrate) Buccal Tablet

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Zelapar

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Prepared by lyophilization

Placed on the tongue where it rapidly dissolves- absorption is buccal, avoid food and liquid 5 min before and after

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Fentora

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Placed between the cheek and gums where disintegration occurs rapidly

Uses Oravescent ® drug delivery system

Oravescent technology involves release of CO2, with pH changes that favor dissolution, then absorption

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Oravescent technology

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1. pH decreases, thus favoring ionized form and dissolution

2. pH then increases, thus favoring unionized form and absorption

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Some general guidelines for administering buccal or sublingual tablets

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Avoid eating, drinking, chewing, smoking, and talking (if practical)

DO NOT DISTURB