Within the oral mucosal cavity, the buccal region offers an attractive route of administration for systemic drug delivery. The mucosa has a rich blood supply and it is relatively permeable.  The buccal mucosa offers several advantages for controlled drug delivery for extended periods of time. The mucosa is well supplied with both vascular and lymphatic drainage and first-pass metabolism in the liver and pre-systemic elimination in the gastrointestinal tract are avoided. The area is well suited for a retentive device and appears to be acceptable to the patient. With the right dosage form design and formulation, the permeability and the local environment of the mucosa can be controlled and manipulated in order to accommodate drug permeation.  Buccal drug delivery is a promising area for continued research with the aim of systemic delivery of orally inefficient drugs as well as a feasible and attractive alternative for non-invasive delivery of potent peptide and protein drug molecules. In 2014, sales of Suboxone sublingual film totalled approximately $1.3 billion in the U.S. while the total market grew to more than $1.7 billion, driven by a 11 percent increase in prescriptions. In 2014, Bunavail buccal film has received US approval which has similar bioavailability of suboxone with half of the dose of buprenorphine.

Other than drugs used for local actions (antifungal, antiviral), generally controlled substances like buprenorphine, naloxone and fentanyl are preferred to release the drug through buccal formulations. However, testosterone (striant) to treat low testosterone levels in men also approved through use of buccal system of delivery. In the US, drugs such as Isosorbide dinitarte, ergoloid delivered sublingually have been discontinued and nitroglycerin has been replaced with sublingual metered spray. Ergomar (ergotamine tartarate) marketed by Rosedale therapeutics is the only sublingual tablets available in the US market, priced $15 per pill.  Subsys (fentanyl) developed by Insys therapeutics was the recent sublingual spray approved in the US for the treatment of breakthrough cancer pain.

Global pharma companies such as Biodelivery Sciences, Bioalliance pharma (Onexo), Meda pharma, Orexo, Generex, Teijin are actively involved in developing oral mucoadhesive buccal delivery systems while sublingual technology have been used by Teva, Sun pharma, Grunenthal, Neurax, Angelini, Sandoz, Ethypharm, Arrow generics, Purdue and Actavis pharma. Sublingual spray technology have been employed by the companies such as Insys therapeutics, Perrigo, Mist pharm, Regency, Novadel, Generex, GW Pharma and Pohl Boskamp in developing potential drugs for the patients.

Ease of administration and better compliance offered by delivering through buccal route offers advantages for patients and physicians over other Invasive route and oral ingestion will drive the market further in positive directions going forward. Novel buccal delivery such as soluble thin films, mucoadhesive films and rapidmist spray offers newer route of delivery for the generics that has lesser patients compliances.

This report will provide detailed analysis on buccal delivery systems in broader pharma market in finding companies and technologies and complexities involved in developing this unique high potential delivery system

Companies Mentioned

Actavis, Angelini, Applied Pharma Research, Ardana Biosciences, Auxillium Pharma, Barr, Biodelivery Sciences, Blue fish, Cynapsus Pharma, Ethypharm, Galena, Galenica, Generex, Grunenthal, Indivior, Insys Therapeutics, IntelGenx , Intellidrug, LTS Lohmann, Meda Pharma, Mist Pharma, Mystic Pharma, Neuraxpharm, Novadel, Novel Labs, Nycomed, Onexo, Oriform, Purdue, Rosedale Therapeutics, Roxane, Sandoz, Sanofi, Snoreeze, Tapemark, Tesa Labtec Pharma, Teva

1. Introduction

2. Types of dosage forms

3. Transmucosal Delivery Systems: The Mouth

4. Potential Benefits of Buccal Films

5. Limitations and Challenges of Buccal delivery system

6. Buccal Films
Formulation aspects
Ideal Characteristic of drugs/excipients for developing Buccal delivery formulations
Manufacturing Methods
Solvent casting method
Hot-melt extrusion
Semisolid casting
Solid dispersion
Rolling
Physico-Chemical Evaluation of Buccal Films
Marketed Buccal Films
Technologies used in Buccal/Sublingual films
BEMA
PharmaFilm

7. Buccal Tablets
Lauriad mucoadhesive technology (Onexo)
OraVescent Technology (Cima Labs)

8. Sublingual films/Tablets
Buccal/ sublingual formulations approved in the US including generics
Buccal/ sublingual formulations discontinued in the US
Buccal/ sublingual formulations underdevelopment worldwide
Buccal /sublingual formulations approved in Europe

9. Other technologies used in buccal delivery systems
ArisGen Pharma  (ArisCrown technology)
Mystic Pharma (VersiDoser powder technology)
Uluru (OraDisc Technology)
Tesa labtec (PerioPatch) – buccal patch
Intellidrug (Intraoral drug delivery device)
Generex Pharma (RapidMist Technology)
Insys therapeutics (sublingual spray)

10. Oral Thin fast Dissolving Films (OTF) –Ideal Characteristics, Classification and Evaluation
Auxillium Pharma (PharmForm Tech)
LTS Lohmann OTF
IntelGenx OTF
Tapemark Solustrip technology
Applied Pharma Research/Tesa Labtec – RapidFilm Technology
Tesa Labtec Pharma  -Mucofilm
Cynapsus Pharma – Sublingual thin film
Seoul Pharma -SmartFilm
Other patented approaches
XGel film
Soluleaves
Wafertab
Foamburst
Micap

List of Tables

Table 1: List of Approved formulations in mucoadhesive systems worldwide
Table 2: List of Marketed Mucoadhesive Drugs Developed Outside the US
Table 3: List of USFDA approved Buccal formulations
Table 4: List of Sublingual Delivery Formulations Approved by the USFDA
Table 5: List of Discontinued Buccal And Sublingual Formulations from the US market
Table 6: List of Sublingual Formulations Approved in Europe
Table 7: List of Buccal Formulations Approved in Europe
Table 8: List of Mucoadhesive delivery drugs under clinical development
Table 9: Classification of Oral Fast Dissolving Technologies
Table 10: Approved Formulations using Oral Thin Film Technologies
Table 11: Physico-chemical Properties of Mucoadhesive Wafers (Oral Thin Films)

List of Charts:

Chart 1: Drug in Mucoadhesive Thin Film Matrix
Chart 2: Ideal properties of Mucoadhesive polymers
Chart 3: Buccal and Oral Delivery of Peptides through Ariscrown
Chart 4: Oral Peptide Delivery Pipeline from ArisGen Pharma
Chart 5: VersiDoser from Mystic Pharma
Chart 6: Clinical profile of Oral-Lyn in Comparison with Humulin (LLY)