Introduction
Oral delivery is currently the gold standard in the pharmaceutical
industry where it is regarded as the safest, most convenient and most economical method of drug
delivery with the highest patient compliance. The tablet is the most widely utilised oral
dose format. A novel tablet concept which offers ease of oral administration and benefits of
increased patient compliance is an orodispersible tablet. This tablet format is designed to readily
dissolve or disintegrate in the mouth generally within <60 seconds without chewing and without
water. A number of orodispersible tablets are commercially available for human use
using technologies developed by pharmaceutical companies such as Cardinal Healthcare, Jannsen
Pharmaceutical, Bioavail,Cima, Eurand and Yamanouchi. These technologies produce
orodispersible tablets which have purposely low mechanical strength to facilitate their fast
disintegration in the mouth. A major limitation of this low mechanical strength of the tablets is the
requirement of specialized costly packaging to protect the tablets and maintain robustness for
administration. A second limitation of the commercialised competitor technologies is the addition of
effervescent or highly water soluble disintegrants which require controlled processing
environment in addition to storage and packaging constraints.
The School of Pharmacy at the Royal College of Surgeons in Ireland
has addressed the above shortcomings by developing a novel formulation and a cost effective
one step manufacturing process using conventional tabletting technology for the production
of mechanically strong orodispersible tablets which are suitable for conventional
packaging. This novel and simple formulation does not require the use of effervescent excipients or
a disintegrant and yet produces rapid dissolving tablets with comparable or faster
disintegration profiles relative to competitor technologies. Using RCSI’s novel formulation and
process, orodispersible tablets do not require to be processed under humidity controlled environment.
RCSI’s proprietary technology is applicable to a wide range of therapeutic agents
including generics, thereby adding value, i.e. “supergenerics” for veterinary or human
application. RCSI’s novel orodispersible formulation may also be applied to
deliver therapeutic agents through the buccal mucosa directly to the systemic circulation
thereby avoiding first pass metabolism offering an added advantage for therapeutic agents which
have poor permeability and oral bioavailability. The oral drug delivery market was estimated to be worth $35bn in
2006 and forecast to reach $52bn by 2010 with a CAGR of 10%. Of this, the orodispersible
tablets, taste masked and micro emulsion formulation segments constitute a 22% share with an
expected CAGR of 17% to 2010. There is a clear opportunity for new enhanced oral products arising
within this market segment. With a growing elderly population, oral technologies and products
which offer ease of administration and cost benefit are expected to stimulate the
market for oral delivery.
RCSI Page 2
Technology
Approximately one-third of the population, primarily the geriatric
and pediatric populations, has swallowing difficulties, resulting in poor compliance with oral
tablet drug therapy which leads to reduced overall therapeutic effectiveness. A new tablet dosage
format, the orodispersible tablet, has been developed to offer the combined advantages of ease
and convenience of dosing in the absence of water or fluid. These tablets are designed to
dissolve or disintegrate rapidly in the saliva generally within 1 minute (range of 5- 50 seconds). Due
to the constraints of the current technologies as highlighted here, there is an unmet need
for improved manufacturing processes for rapid orodispersible tablets that are mechanically
strong, allow for ease of processing, handling and packaging with production costs similar to
that of conventional tablets to allow application to a wider range of
actives.
Applications
Formulation advances using a conventional tabletting process have
led to the development of mechanically robust tablets which readily dissolve/disintegrate
within <50 seconds and can be formulated in a range of sizes from 10 - 15mm. The tablets produced
are stable, and can withstand shipment in conventional tablet containers without loss
of integrity. A number of orodispersible products for human and veterinary administration are
currently under development at RCSI for the delivery of water soluble, lipophilic
as well as poorly permeable therapeutic compounds. A number of these formulations have been
scaled up and are at the stage of evaluation in a phase I pharmacokinetic study in human
volunteers.
Advantages
·
Lower production, packaging and distribution costs compared to
current commercially
available products;
·
Versatile technology suitable for the development of enhanced
products for veterinary
medicines, OTC, Rx medicines and line
extensions;
·
New proprietary method allows for enhanced systemic absorption of
actives from buccal
mucosa;
·
New proprietary method allows for the incorporation of
microencapsulated drugs for
enhanced bioavailability, flexibility of dosing and immediate
and/or controlled release for
superior therapeutic benefit.
Contacts:
Dr. Gearóid Tuohy, RCSI Technology Transfer Office, 123 St
Stephen’s Green, Dublin 2, Ireland; email:
gearoidtuohy@rcsi.ie Tel: +353 1
4022362
Dr Aoife Gallagher, RCSI Technology Transfer Office, 123 St
Stephen’s Green, Dublin 2, Ireland; email:
aoifegallagher1@rcsi.ie. Tel: +353 1
4022394;
Principle
Investigator:
Dr. Zeibun Ramtoola, School of Pharmacy, Royal College of Surgeons,
123 St Stephen’s Green, Dublin 2,
Ireland. Email: zramtoola@rcsi.ie Tel: +353 1 40228626 or +353 1
4022498