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MIXING ODONTOPASTE
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In the literature it is common to find references to the mixing of calcium hydroxide in a 50:50 ratio with Odontopaste or Ledermix Paste. Odontopaste is premixed with calcium hydroxide at ~0.25% - 0.50%. The addition of additional calcium hydroxide to Odontopaste is no longer recommended by ADM. We cannot speak on behalf of Ledermix but the test results make it clear that Ledermix mixed with calcium hydroxide is not ideal if the steroid effect is required. If you are seeking the steroid effect then mixing Odontopaste with additional calcium hydroxide defeats the purpose. The steroid is destroyed rapidly and the antibiotic is also affected albeit over a far longer time period of weeks. |
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The tests were performed independently by a TGA
accredited laboratory. No person
associated with ADM in any way was involved in the testing other than
with the design. The above graph illustrates the effect Pulpdent has on
the steroid component of Odontopaste and Ledermix Paste. |
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The problems with the Paul Abbott studies. Much of the testing of the mixing of Ledermix with calcium hydroxide was performed by Paul Abbott along with Geoff Heithersay and Rory Hume in the mid 80's at Adelaide University. It is easy to be critical of the work performed some 20 years later but this is not the purpose of this explanation. However there are obvious errors which need to be addressed. This explanation is a summary of our test findings and the implications that they have on the 50:50 mixing protocol which has been long recommended. If further details are required feel free to contact ADM directly. These findings have not been submitted in the form of an article to be published in the ADJ however they will be in the future. In Paul Abbott's studies, the concentrations of the active ingredients of ledermix paste(demeclocycline hydrochloride and triamcinolone acetonide) when mixed with Pulpdent in a 50:50 ratio were determined by placing a known amount of radioactively labeled tetracycline or triamcinolone acetonide (not together) in a known amount of Ledermix Paste. A scintillation counter was used to measure the radioactivity which correlated to the amounts diffused through the tooth. From the counts a determination/extrapolation was made of the concentration of the ingredients. However the authors never took into account the chemistry between the ingredients. So any measurements taken, relied on radioactivity alone and were not related to the type of molecule. Hence any breakdown of the antibiotic or steroid was not considered. The study was not designed to detect the chemistry of the interactions of calcium hydroxide and Ledermix paste yet made conclusions assuming that was there was no breakdown of the steroid or antibiotic. There was no validation to prove that the radioactive labeling correlated with the concentrations of the steroid and antibiotic when mixed 50:50. This is where the study fell down. What was measured was the radioactivity of breakdown by-products of the antibiotic and steroid depending on which was labeled along with any unaffected labeled molecules. Therefore when measuring the amount of triamcinolone acetonide in a 50:50 mix with Pulpdent, Paul Abbott's method could not distinguish between the breakdown by-products and the triamcinolone acetonide molecule as a whole. As a result the diffusion studies were incorrectly interpreted. ADM used modern HPLC with validated methods for detection of clindamycin hydrochloride, demeclocycline hydrochloride and triamcinolone acetonide. These methods were developed for TGA, were part of the approval process in gaining registration and were fully examined as part of the TGA audit. They have not been peer reviewed by dentists but they have been peer reviewed by experts within TGA. The focus of the testing was the chemistry and interaction of the ingredients. Hence there was no need to perform tests within teeth. In these tests we found that the steroid was almost immediately destroyed. In Ledermix almost 80% of the steroid was destroyed at the point of mixing i.e. zero time point. In Odontopaste the initial effect was approximate to the halving of the concentration which is to be expected as 50% is now made up of Pulpdent (Pulpdent is 40% Ca(OH)2 - in the batch we used it was 19.2%). Nonetheless even with Odontopaste optimised for the use of calcium hydroxide, at the 72 hour time point the amount of triamcinolone acetonide was less than 0.2%. At this present time no therapeutic threshold has been proven to exist so it is improper to consider this as subtherapeutic. However, even after all our efforts to improve the longevity of the steroid component, we nonetheless felt we could no longer recommend the use of pulpdent or Ca(OH)2 with Odontopaste. Our testing also showed that the 50:50 mixing of Ledermix with calcium hydroxide as recommended by Paul Abbott et al is not justified. There is no science to back it up and in fact our tests prove otherwise. Furthermore there have been no tests performed on the byproducts which are produced in the breakdown of Ledermix Paste with calcium hydroxide. Tetracyclines are known for producing toxic breakdown products and in any guide for pharmaceuticals there will always be a warning that expired tetracyclines should not be taken for this very reason. There has been no testing to determine if in fact the 50:50 mixing of tetracycline with calcium hydroxide does have a similar effect on the tetracycline component. To assume it is safe without testing is inappropriate. The breakdown products of Odontopaste mixed with Pulpdent have been tested and results have shown that no latent toxicity is produced. Once again this testing has not been performed with Ledermix and Pulpdent and as such the toxicity of the mix and the breakdown products remains unknown. We continue to test and develop better formulations. As we work to ISO 13485 guidelines, we start from first principles and test everything. Every possible problem is initially identified in a thorough risk analysis and then we undertake repeated testing to confirm the results. It is only from this thorough approach that we can be confident that the products we produce are safe. All the results for the testing will be submitted for publishing. The results are interesting and worthy of getting an early airing. The addition of calcium hydroxide to Odontopaste or Ledermix Paste destroys the steroid. It does not enhance the steroids pharmaceutical activity as claimed by some. Let's look at some of the statements made. 1. "It has been shown that the 50:50 mixture results in slower release and diffusion of the active components of Ledermix Paste which makes the medicament last longer in the canal" Abbott PV, Hume WR, Heithersay GS. Effects of combining Ledermix and calcium hydroxide pastes on the diffusion of corticosteroid and tetracycline through human tooth roots in vitro. Endo Dent Traumatol 1989;5:188-192. 2. "It has been shown that the 50:50 mixture results in slower release and diffusion of the active components of Ledermix paste which makes the medicament last longer in the canal. This in turn helps to maintain the sterility of the canal for longer and also maintains a higher concentration of all components within the canal”. 3. “It has been shown that the 50-50 mixture results in slower release and diffusion of the active components of Ledermix paste, which makes the medicament last longer in the canal. This in turn helps to maintain the asepsis of the canal for longer and also maintain a higher concentration of all components within the canal”. Mohammadi Z, Abbott P. On the local application of antibiotics and antibiotic-based agents in endodontics and dental traumatology. Int Endod J. 2009 Jul;42(7):555-67. These statements are clearly incorrect. Calcium hydroxide does not maintain a higher concentration of all components within the canal. No valid studies have shown this to be accurate. The interactions between calcium hydroxide and Ledermix paste are poorly understood and remain as such. There is no information as to what the interactions produce. Ignorance of this fact does not make the product safe. So if calcium hydroxide is bad for the paste why does ADM include it in Odontopaste? The level of calcium hydroxide in Odontopaste ranges between 0.25% to 0.50%. This is an exceptionally low amount. We did initially have calcium hydroxide present at 2% levels but our testing confirmed that even at 2% the triamcinolone acetonide was affected. Below is a direct HPLC graphing of the effect of 0.5% calcium hydroxide and 2.0% calcium hydroxide on Odontopaste.
We did so, not without some issues, but we have now successfully replaced triethanolamine with calcium hydroxide. This is one of the reasons Odontopaste contains calcium hydroxide. The calcium hydroxide within Odontopaste interacts with the other ingredients in such a way as to not greatly increase the pH. Hence any issue with inflammatory reactions, particularly in avulsed or traumatised teeth, to Odontopaste due to the inclusion of calcium hydroxide, is highly unlikely as the there is no free calcium hydroxide present. The second reason we included calcium hydroxide in Odontopaste is that we received feedback from dentists who continue to use the 50:50 protocol that when Odontopaste and calcium hydroxide (Pulpdent) were mixed, the resulting paste had a marked change in viscosity. By adding a trace amount of calcium hydroxide to the paste we prevented this from occurring. We trust that the above explanation goes some way into bringing some science into what really occurs when mixing calcium hydroxide with Odontopaste or Ledermix paste. Although mixing calcium hydroxide with Odontopaste is safe we can no longer justify recommending the practice and suggest that when dentists use Odontopaste, to do so without mixing it with calcium hydroxide if the steroid effect is required. The antibiotic, clindamycin hydrochloride, can sustain the high pH for a period of time (weeks) however it too eventually succumbs. However, there are no toxic breakdown products produced when calcium hydroxide is mixed with Odontopaste. Finally, Odontopaste does not stain teeth. Ledermix paste stains teeth. This alone should preclude the use of Ledermix. Suggesting that subgingival application of Ledermix paste somehow negates the problem is a poor alternative solution. A better solution is to not use Ledermix at all. |
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