Comparison of properties on Orally Disintegrating Tablets (ODTs) produced by direct compression or fluid bed granulation

Abstract

Orally disintegrating tablets (ODTs) is a popular drug delivery system as they dissolve in the
mouth, usually within seconds which enables easy medication for patients with problem
swallowing. In this thesis properties of ODTs were compared when produced with direct
compression of the excipients or the excipients were pretreated to form granules in a fluid bed
granulator prior to tableting.
By altering the excipients used and the process parameters during fluid bed granulation it was
concluded that the choice of polyol as the main filler in the tablet mostly affected the
properties of both the granules and the produced tablets. This was also concluded for the
tablets produced with direct compression. The granulation process increased the flowability of
the particles.
The disintegration time was also mostly affected by the filler and not the used super
disintegrants. Tablets containing mannitol disintegrate faster than tablets with isomalt or
xylitol and is also less friable. From the measured in vivo disintegration times an in vitro
method was developed with the aim to give a better in vitro-in vivo correlation (IVIVC)
compared to existing methods. The developed method is applicable for tablets containing
mannitol as they swell when disintegrating. For this a texture analyzer was used which
applied and measured the force on tablets when swelling.

Popular Abstract

Today, one of the most common drug delivery system is oral tablets. Tablets can either be
swallowed, chewed or dissolved in the mouth, also called orally disintegrating tablets (ODTs).
The advantage of ODTs is the fast disintegration time, usually within seconds to minutes in
the mouth, which enables easy medication for patients with trouble swallowing. The
disintegration time can be altered by using different excipients in the tablets.
In this thesis the production method and added excipients was altered to evaluate the effect on
the disintegration time and how fragile the tablets are. The tablets were produced with
excipients in powder form and excipients pre-treated with fluid bed granulation to produce
larger particles called granules. The granules formed tablets less susceptible to attrition
compared to tablets produced with powders. However, the disintegration time was similar for
tablets produced with either method. More importantly the excipients affected the
disintegration time, the fastest disintegration was detected with tablets containing mostly
mannitol or isomalt. Super disintegrants are excipients added to speed up the disintegration
time as they help disrupting the tablet’s structure. Comparing three different super
disintegrants it was concluded that they all gave similar disintegration times, however
crospovidone had a faster in vivo disintegration time compared to the other two.
The granules were also compared when produced with different excipients and with different
air flow and spray rate during granulation. In conclusion the more soluble excipients such as
isomalt and xylitol produced larger granules. An advantage of using granules instead of
excipients in powder form, when producing tablets is that the flowability of the particles
increases. This can decrease the friction on the equipment during production and also
decrease the segregation of particles.
The disintegration time may be measured in vivo, by placing the tablet in the mouth or in vitro
using a water bath. Current standards use the water bath method to determine the
disintegration time for ODTs. However, the drawback of this method is the poor similarity to
the conditions in the mouth. With the aim to give a disintegration time more correlated to the
in vivo disintegration time, a new method was developed to measure the disintegration time of
ODTs. The method uses a texture analyzer which measure the swelling of the tablet once in
contact with liquid. It was determined that the in vivo disintegration time equals the time of
swelling with a factor 2.5. This method was appliable for tablets containing mainly mannitol
as they had a swelling disintegration mechanism. Tablets with more soluble excipients such as
isomalt and xylitol had no swelling mechanism, instead they melted, and the disintegration
time couldn’t be measured with the same method. To develop a method measuring the in vitro
disintegration time for tablets melting in contact with liquid, a continuous stream of liquid in
combination with a descending probe would probably be necessary. The descending probe
should be able to measure the disintegration time as the tablets melt in contact with liquid.

• author: Ahlbom, Julia
• supervisor: Lars Nilsson; Elin Oscarsson; Hanna Forsström
• organization: Food Technology and Nutrition (M.Sc.)
• course: KLGM15 20231
• year: 2023
• type: H2 - Master's Degree (Two Years)
• subject: Technology and Engineering
• keywords: Orally disintegrating tablet, fluid bed granulation, disintegration time, pharmaceutical technology
• language: English
• id: 9128894
• date added to LUP: 2023-06-22 11:20:57
• date last changed: 2023-06-22 11:20:57