Selecting the Best Platform for Optimization of ODT Disintegration Time

Situation

Orodispersible Tablets or Orally Disintegrating Tablets (ODTs) are of growing interest as delivery systems for the  administration of active ingredients in pharmaceutics and nutraceutics. ODTs are a patient-friendly alternative to the traditional “tablet and a glass of water” as they disintegrate quickly in the mouth. This simple and convenient administration makes ODTs a key player in the battle to achieve patient compliance, particularly suitable for pediatric, geriatric and psychiatric patients.(1)

Challenge

The aim of this study was to compare four commercial ODT platforms based on their ability to reach fast oral disintegration times. The disintegration time of the resulting ODTs from these platforms was tested by three separate methods in order to analyze the reproducibility of in vivo results against in vitro.The aim of this study was to compare four commercial ODT platforms based on their ability to reach fast oral disintegration times. The disintegration time of the resulting ODTs from these platforms was tested by three separate methods in order to analyze the reproducibility of in vivo results against in vitro.

Solution

Materials

The composition of the ODT platforms evaluated is described in Table 1.

Table 1

Method

Preparation of the tablets
300 mg tablets were prepared by blending the ODT platform (P1, P2, P3 or P4) (99%) and the lubricant magnesium stearate (1%), for 3 minutes in a TURBULA® blender. The blend obtained was then compressed using a press simulator, STYLCAM® 200R, allowing a good simulation of the formulation's behavior in an industrial environment. The tablets were compressed at hardness of 50 N and 90 N at a tableting speed of 40500 tab/h using flat circular punches of 10 mm. The rotary press simulated was a Fette 2090i.

ODT characterization

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Disintegration time evaluation 

EP-Method: 

• The disintegration time was evaluated using the following EP 8.5 protocol. 6 tablets from each platform were placed individually in the 6 tubes of the basket without the addition of discs. The apparatus filled with water as immersion fluid was maintained at 37 ± 2°C. The
  disintegration time (s) of each group of tablets was considered as the time necessary for the total disintegration of all the units tested.

Instron method (Developed by Roquette):

• In order to closely simulate the patient experience, Roquette has developed its own in vitro method using a texturizer Instron. The tablet is placed in a small cell, and an initial force of 3.7 N is applied on the tablet. 2 mL of water is then added, with the “time of collapse” being recorded. This “time of collapse” is measured as the time taken for the initial 3.7 N force to decrease to 1.5 N, indicating that the tablet has fully disintegrated.

In vivo method:

• The most popular in vivo method requires a tasting with trained panelists, standardized protocol, and controlled conditions. The complete oral disintegration time of the ODT is recorded during the session of tasting.

 

Results

The EP in vitro disintegration time for both hardness (50 N and 90 N) is shown in Figure 1. PEARLITOL® Flash (P1) developed by Roquette displayed the shortest disintegration times, around 25 s, regardless of tablet hardness. Platforms P2 and P3 containing the superdisintegrant crospovidone showed by far the highest disintegration times, and also a  high sensitivity to tablet hardness. For instance, platform P3 showed a disintegration time of 39 s at 50 N, and 248 s at 90 N. Platform P4 containing the superdisintegrant sodium croscarmellose did not display a sensitivity to tablet hardness, but still displayed higher disintegration times than PEARLITOL® Flash.

Figure 1. EP disintegration times of ODTs (50 N and 90 N) made from different marketed ODT platforms.

When the Instron method of Roquette was used, PEARLITOL® Flash (P1) maintained its very low disintegration time, regardless of tablet hardness. As shown in Figure 2, platforms P2 and P3 again showed very high disintegration times, with platform P3 showing a particularly high sensitivity to tablet hardness. Platform P4 displayed higher disintegration times than those obtained with PEARLITOL® Flash as well as higher disintegration times in comparison with those obtained by the EP method: 65 s versus 43 s at 50 N. Using both these methods,
we can observe that the use of superdisintegrants does not systematically allow fast disintegration of the ODTs.

Figure 2. Instron disintegration times of ODTs (50 N and 90 N) made from different marketed ODT platforms.

Finally, with disintegration times of 36 s and 40 s at 50 N and 90 N, the in vivo tests indicate that PEARLITOL® Flash disintegrates faster than the other tested ODT platforms. In addition, the in vivo testing confirms that ODTs made from PEARLITOL® Flash are not sensitive to the hardness of the tablet.

Also, this analysis of disintegration time confirms the in vitro-in vivo correlation for this platform (Figure 3). Surprisingly, platform P2 showed lower disintegration times (58 s and 82 s) in comparison to results from both the EP method (136 s and 259 s) and the Instron method (>149 s). This would seem to indicate that there is no in vitro–in vivo correlation for this platform. In vivo Platform P3 and P4 displayed the highest disintegration times, and platform P3‘s sensitivity to tablet hardness was confirmed.

Figure 3. In vivo disintegration times of ODTs (50 N and 90 N) made from different marketed ODT platforms

The quickest in vitro and in vivo disintegration times demonstrated by PEARLITOL® Flash can be explained by its higher wettability. The wettability of a tablet is known to be a critical factor impacting disintegration time; thus, the penetration index as function of time was used to compare PEARLITOL® Flash against two other platforms containing either crospovidone or croscarmellose (Figure 4).

Figure 4. Penetration index vs time of ODTs made from platforms without (PEARLITOL® Flash) or with superdisintegrants.

The penetration index is defined as the quantity of water taken up by the tablet, and its evolution over time can be used as an indicator of the wettability of the tablet. The higher the slope displayed, the faster the water penetration into the tablet. This in turn indicates a higher wettability which allows a shorter disintegration time. Therefore, the ODT formulations containing superdisintegrants crospovidone or croscarmellose have a lower wettability, and thus disintegration will be slower than PEARLITOL® Flash ODTs which contain no superdisintegrant.

Conclusion

PEARLITOL® Flash is a ready-to-use directly compressible platform which allows very fast oral disintegration times. In addition, we have also shown that the disintegration time of PEARLITOL® Flash in terms of robustness was superior to the other ODTs platforms tested. Finally, the disintegration time of ODTs made from PEARLITOL® Flash demonstrated a good in vitro–in vivo correlation.

References

1. Fu Y., Yang S., Jeong S. H., Kimura S., Park K. Orally Fast Disintegrating Tablets: Developments, Technologies, Taste-Masking and Clinical Studies. Critical Reviews™ in Therapeutic Drug Carrier Systems, 21(6):433-75 (2004).
2. European Pharmacopeia 8.5. edQm. General Chapters, 809-11. December 2014

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