|Year : 2018 | Volume
| Issue : 2 | Page : 169-174
Analysis of cariogenic and erosive potential of pediatric antiepileptic liquid medicaments: An In vitro study
M Deepthi, Mallayya C Hiremath, SK Srinath, J Nagarathna
Department of Pedodontics and Preventive Dentistry, Government Dental College and Research Institute, Bengaluru, Karnataka, India
|Date of Submission||22-Jan-2018|
|Date of Acceptance||24-Apr-2018|
|Date of Web Publication||24-May-2018|
Dr. Mallayya C Hiremath
Department of Pedodontics and Preventive Dentistry, Government Dental College and Research Institute, Fort, Bengaluru - 560 002, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: Epilepsy affects seventy million people worldwide. India accounts for 10%–20% (5–10 million) of the global burden of epilepsy. The prevalence of dental caries is significantly higher in epileptic children. Antiepileptic pediatric liquid medicaments (PLMs) are commonly prescribed and are easily accepted by children. However, these drugs can place children at risk for dental caries and dental erosion, when used on a regular basis and over a long period. Aim: The aim of this study was to analyze the cariogenic and erosive potential of pediatric anti-epileptic LMs. Material and Methods: Ten pediatric antiepileptic LMs which are most commonly used in children for a prolonged period were obtained from local pharmacies after consulting pediatricians of Bengaluru city. Physicochemical analysis for endogenous pH, viscosity, and sugar content of these antiepileptic PLMs was done. Data obtained were subjected to statistical analysis using SPSS software. One-way ANOVA, post hoc test, and t-test were used for the statistical analysis. Results: Most of the antiepileptic PLMs analyzed showed low pH, high viscosity, and higher total sugar content. Statistically significant differences (P = 0.001) were found among the PLMs in terms of pH, viscosity, and sugar content. Conclusions: Most of the antiepileptic PLMs showed cariogenic and erosive potential. Thus, the study highlights the need to reformulate the antiepileptic PLMs with sugar substitutes or making it sugar free.
Keywords: Antiepileptics, dental caries, epilepsy, liquid medicaments, tooth erosion
|How to cite this article:|
Deepthi M, Hiremath MC, Srinath S K, Nagarathna J. Analysis of cariogenic and erosive potential of pediatric antiepileptic liquid medicaments: An In vitro study. J Indian Assoc Public Health Dent 2018;16:169-74
|How to cite this URL:|
Deepthi M, Hiremath MC, Srinath S K, Nagarathna J. Analysis of cariogenic and erosive potential of pediatric antiepileptic liquid medicaments: An In vitro study. J Indian Assoc Public Health Dent [serial online] 2018 [cited 2022 Jun 30];16:169-74. Available from: https://www.jiaphd.org/text.asp?2018/16/2/169/233072
| Introduction|| |
Dental caries is the most common chronic disease in children. It is about five times as common as asthma and seven times as common as hay fever. Similarly, epilepsy is also a common chronic neurologic disorder that affects 1%–3% of the population and almost 10% of the population will have one or more seizures at some time in their lives. Chronically ill young children receive a variety of oral liquid medications for improvement or maintenance of health. In almost all aspects of oral health and dental status, the condition of patients with epilepsy is significantly worse than that of age-matched groups in the general (nonepileptic) population.
Treatment of epilepsy is emphasized not only on improving the quality of life by minimizing the seizures but also by reducing the side effects of medications used in its treatment. In pediatric patients, most commonly used medicaments are in liquid form due to their easy acceptance by children.,, Pediatric liquid medicaments (PLMs) are used either for short durations in conditions such as cough, cold, or fever or for prolonged period in chronic diseases such as epilepsy, asthma, or psychiatric disorders. Most LMs are for children and are usually colored, flavored, and sweetened with various additives. The most common sweetener bases for medication include sucrose, sorbitol, and saccharin. Sucrose acts as a preservative and an antioxidant.
Studies on cariogenicity and erosive potential of PLMs are very few.,,, However, there are no studies on the cariogenicity and erosive potential of antiepileptic PLMs.
Hence, it is very essential to know the cariogenicity and erosive potential of these LMs. Hence, the purpose of this in vitro study was to evaluate the cariogenicity and erosive potential of antiepileptic PLMs by analyzing the pH, viscosity, and total sugar content.
| Materials and Methods|| |
Ethical approval was obtained from the institutional ethical committee (Ref no. GDCRI/ACM (2)/07/2016-17). Ten antiepileptic PLMs which are most commonly used in children for a prolonged period were obtained from local pharmacies after consulting pediatricians of Bengaluru city. The samples were selected based on the following inclusion and exclusion criteria:
- Inclusion criteria: Pediatric antiepileptic LMs which are commonly used for a long duration
- Exclusion criteria: Pediatric antiepileptic LMs which are banned for use in children.
A total of ten samples [Figure 1] containing two each of the following antiepileptic generic drugs were selected:
- Phenytoin (sample-1; Eptoin, sample-2; Dilantin)
- Sodium valproate (sample-3; Valparin, sample-4; Valpex)
- Carbamazepine (sample-5; Oxcarbazepine, sample-6; Tegrital)
- Levipil (sample-7; Levipil, sample-8; Levroxa)
- Phenobarbitone (sample-9; Gardenal, sample-10; Barbinol).
Method of study
Physicochemical analysis ,, for endogenous pH, viscosity, and total sugar contents of all the ten pediatric antiepileptic LMs was carried out in the Biochemistry and Pharmacy laboratories of Government College of Pharmacy, Bengaluru, and Government Central Pharmacy, Bengaluru. The pH of each LM was determined using a Eutech digital pH meter [Figure 2]. All the readings were taken in triplicate and at room temperature.
The viscosity was measured in centipoises (cP) using a calibrated digital Brookefield rotational viscometer [Figure 3]. A suitable spindle (no. 3) was chosen and the reading was recorded. Viscosity of each LM was later calculated using the following formula:
Viscosity in cP = dial reading × factor (for spindle no: 3, factor 10).
Analysis of total sugar content was done by volumetric method  (Fehling's test). Sample was prepared by accurately measuring 10 ml of antiepileptic PLM and adding 10 ml of concentrated hydrochloric acid. It was kept aside overnight for acid hydrolysis which breaks down sucrose into glucose and fructose. Later, it was neutralized with approximately 1M sodium hydroxide and made up to 100 ml in a volumetric flask. The total sugar content was determined by titrimetric method [Figure 4]. Sugar g/100 ml was calculated using the following formula:
Sugar g/100 ml =
Feq: Equivalence factor
Vtitration = Titration volume required for the sample.
Data obtained were subjected to statistical analysis using Statistical Package for the Social Sciences (SPSS) software version 22 (IBM, Chicago). Data were presented by means of descriptive statistics (mean and standard deviation). Data analysis was done using one-way ANOVA, Bonferroni post hoc test, and t-test.
| Results|| |
Around 70% of the tested pediatric antiepileptic LMs had a pH below 5.5, with syrup oxcarbazepine having the least pH (3.08 ± 0.005). A pH of 5.5 is traditionally considered to be the “critical pH” for enamel demineralization. Viscosity of antiepileptic PLMs ranged from 24.33 ± 1.15 to 573.33 ± 10.41 cP, with dilantin having the highest (573.33 ± 10.41) viscosity. Total sugar content of anti-epileptic PLMs varied between 0.0 ± 0 gm% to 26.63 ± 1.81 gm% [Table 1].
|Table 1: Endogenous pH, viscosity, and total sugar contents of antiepileptic pediatric liquid medicaments|
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The difference was statistically significant (P < 0.001) among the five generic pediatric antiepileptic LMs in terms of pH, viscosity, and sugar content [Table 2].
|Table 2: Comparison of pH, viscosity, and total sugar contents among five generic antiepileptic liquid medicaments|
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[Table 3], [Table 4], [Table 5] show intergroup comparison of pH, viscosity (cP), and total sugar content (gm%), respectively, of antiepileptic PLMs using Bonferroni post hoc test.
|Table 3: Intergroup comparison of pH of antiepileptic pediatric liquid medicaments using Bonferroni post hoc test|
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|Table 4: Intergroup comparison of viscosity (centipoises) of antiepileptic pediatric liquid medicaments using Bonferroni post hoc test|
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|Table 5: Intergroup comparison of total sugar content (g%) of antiepileptic pediatric liquid medicaments using Bonferroni post hoc test|
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| Discussion|| |
Dental caries is a multifactorial disease caused by the interaction between cariogenic bacteria with the appropriate substrate, in a susceptible host, within a certain time. It is the single-most common chronic childhood disease which affects oral health-related quality of life. The study conducted by the National Center for Health Statistics suggests that dental caries is more prevalent than many other systemic diseases including asthma, early childhood obesity, and diabetes. Although the prevalence of dental caries in children has decreased significantly in the past decades in many developed countries, it continues to be a major public health problem, especially in poor and disadvantaged groups of several developing economies.
Children on an average take medicine every 8 h daily or 10 times a week. Moreover, other healthy children who take medicines infrequently and for short periods are also at risk. Many liquid medications have an endogenous low pH  that may itself contribute to demineralization or at least inhibit the demineralization–remineralization process in newly erupted teeth.
Epilepsy is a relatively common problem in children, adults, and the elderly. Dentists need to be familiar with the various manifestations of the disease, the anticonvulsant medications the patients are taking, and the complications and side effects of these drugs. Jovanovic´ and Gajic´ showed that children with epilepsy and their parents had worse habits, attitudes, and behavior toward oral health than that of healthy controls and their parents.
Medicines in the form of syrups intended for pediatric use contain 10%–80% sucrose, on an average about 55%. Maguire et al., in a survey conducted found that the children taking long-term liquid oral medicines had significantly more caries of deciduous anterior teeth than their siblings.
Very few studies are reported about the association between various PLMs and their cariogenicity and erosive potential, but the present study specifically included the antiepileptic LMs because of their long-term usage in children.
People who receive long-term PLMs may be at greater risk of developing tooth decay when they are using sweetened medications. Taken at night they can be an aggravating condition because during this period salivary flow rate is reduced and the time of elimination from the oral cavity is prolonged. Hence, whenever possible, the medicament should be taken during day time or along with meals during night time. Proper oral hygiene practices should be followed. In the present study, total sugar content of anti-epileptic PLMs varied between 0.0 ± 0 gm% to 26.63 ± 1.81 gm% and viscosity ranged from 24.33 ± 1.15 to 573.33 ± 10.41 cP, with dilantin having the highest viscosity.
The pH is an accurate indicator and an important variable in investigating the erosive potential of liquid medicines. In addition to pH and neutralizable acidity, viscosity of the syrup also influences the degree of surface enamel demineralization. Syrups with high viscosity will be retained on the tooth surface for a longer duration leading to enamel erosion.,, Liquid medicines with low pH and high viscosity when administered frequently have greater synergetic potential to cause dental erosion. Around 70% of the tested pediatric antiepileptic LMs had a pH below 5.5, with syrup oxcarbazepine having the least pH (3.08 ± 0.005). A pH of 5.5 is traditionally considered to be the “critical pH” for enamel demineralization. The concept of critical pH was initially applied to indicate the pH at which saliva was no longer saturated with respect to calcium and phosphate ions, thereby permitting hydroxyapatite to dissolve. The critical pH may, therefore, be the pH at which the environment of the enamel becomes unsaturated and at which sufficiently high concentrations of unionized acid are present to ensure the inward diffusion of enough acid to extend the lesion.
In addition to pH, viscosity of the medicated syrups is an important factor to be considered in erosion. In the present study the viscosity of the PLMs ranged from 24.33 ± 1.15 to 573.33 ± 10.41 cP, with dilantin having the highest viscosity. The syrup with high viscosity has more adhesiveness and less flow ability. The greater the adherence of the syrup, the longer will be the contact time with the tooth surface and the higher will be the likelihood of erosion. The ingestion of liquid oral medications at bedtime is frequently not followed by proper oral hygiene. Hence, health professionals should educate the parents and children about the potential risk of dental caries and dental erosion through the use of sugar-containing PLMs.
Limitations of the study
In the present study, only antiepileptic PLMs were analyzed.
Recommendations and suggestions to reduce PLM-related dental caries are as follows:
- Further studies are required to assess the cariogenicity and erosive potential of other long-term used PLMs such as anti-asthmatics, antipsychotics, and multivitamins
- Pediatricians and parents should understand the consequences of sugar-containing PLMs and the importance of maintaining the oral hygiene after the intake of PLMs to prevent dental caries
- All medicines should be labeled with the type of sweetener, whether sugar containing or sugar free. If it is a sugar-containing medicine, it should be labeled with a warning for tooth decay 
- Pharmaceutical companies should consider reducing the sugar content in PLMs or replace them with nonsugar sweeteners such as xylitol, aspartame, and saccharin
- A public health policy must be implemented in order to limit sugars in PLMs or replace them with sugar substitutes.
Parents should be psychologically counseled and empathetically reassured for feeling guilty about the medical condition of their child. They should understand the importance of administering the PLMs and maintaining the oral hygiene.
| Conclusions|| |
Based on the results of the present in vitro study, it can be concluded that:
- Most pediatric antiepileptic LMs tested had acidic pH values which were below the critical pH except sodium valproate and phenobarbitone
- Most pediatric antiepileptic LMs tested had high viscosity
- Most pediatric antiepileptic LMs tested had high total sugar content except phenobarbitone, all of which increase the PLMs' cariogenic and erosive potential.
Thus, children should be encouraged to rinse their mouth with water after taking PLMs and, for children <2 years, oral hygiene practices such as brushing should be strictly practiced by the parents or caretakers. PLMs with sugar substitutes should be considered.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Hauser WA, Annegers JF, Rocca WA. Descriptive epidemiology of epilepsy: Contributions of population-based studies from Rochester, Minnesota. Mayo Clin Proc 1996;71:576-86.
Kiran KJ, Vinay C, Uloopi KS, Sekhar RC, Madhuri V, Alla RK. Erosive potential of medicated syrups on primary teeth: An in vitro
comparative study. Br J Med Med Res 2015;5:525-32.
Károlyházy K, Kovács E, Kivovics P, Fejérdy P, Arányi Z. Dental status and oral health of patients with epilepsy: An epidemiologic study. Epilepsia 2003;44:1103-8.
Nankar M, Walimbe H, Ahmed Bijle MN, Kontham U, Kamath A, Muchandi S, et al.
Comparative evaluation of cariogenic and erosive potential of commonly prescribed pediatric liquid medicaments: An in vitro
study. J Contemp Dent Pract 2014;15:20-5.
Babu KL, Doddamani GM, Naik LR, Jagadeesh KN. Pediatric liquid medicaments – Are they cariogenic? An in vitro
study. J Int Soc Prev Community Dent 2014;4:108-12.
Scatena C, Galafassi D, Gomes-Silva JM, Borsatto MC, Serra MC.In vitro
erosive effect of pediatric medicines on deciduous tooth enamel. Braz Dent J 2014;25:22-7.
Xavier AF, Moura EF, Azevedo WF, Vieira FF, Abreu MH, Cavalcanti AL, et al.
Erosive and cariogenicity potential of pediatric drugs: Study of physicochemical parameters. BMC Oral Health 2013;13:71.
Kulkarni ML, Sureshkumar C, Venkataramana V. Colourings, flavourings, and sugars in children's medicines in India. BMJ 1993;307:773.
Hill EM, Flaitz CM, Frost GR. Sweetener content of common pediatric oral liquid medications. Am J Hosp Pharm 1988;45:135-42.
Bigeard L. The role of medication and sugars in pediatric dental patients. Dent Clin North Am 2000;44:443-56.
Subramaniam P, Nandan N. Cariogenic potential of pediatric liquid medicaments – An in vitro
study. J Clin Pediatr Dent 2012;36:357-62.
de Souza PM, Mello Proença MA, Franco MM, Rodrigues VP, Costa JF, Costa EL, et al.
Association between early childhood caries and maternal caries status: A cross-section study in São Luís, Maranhão, Brazil. Eur J Dent 2015;9:122-6.
Casanova-Rosado AJ, Medina-Solís CE, Casanova-Rosado JF, Vallejos-Sánchez AA, Maupomé G, Avila-Burgos L, et al.
Dental caries and associated factors in Mexican schoolchildren aged 6-13 years. Acta Odontol Scand 2005;63:245-51.
Dye BA, Tan S, Smith V, Lewis BG, Barker LK, Thornton-Evans G, et al.
Trends in oral health status: United states, 1988-1994 and 1999-2004. Vital Health Stat 11 2007;11:1-92.
Neves BG, Farah A, Lucas E, de Sousa VP, Maia LC. Are paediatric medicines risk factors for dental caries and dental erosion? Community Dent Health 2010;27:46-51.
Feigal RJ, Jensen ME. The cariogenic potential of liquid medications: A concern for the handicapped patient. Spec Care Dentist 1982;2:20-4.
Kenny DJ, Somaya P. Sugar load of oral liquid medications on chronically ill children. J Can Dent Assoc 1989;55:43-6.
Gurbuz T, Tan H. Oral health status in epileptic children. Pediatr Int 2010;52:279-83.
Jovanović S, Gajić I. Health habits, attitudes and behavior towards oral health of children with epilepsy. Srp Arh Celok Lek 2007;135:167-73.
Maguire A, Rugg-Gunn AJ, Butler TJ. Dental health of children taking antimicrobial and non-antimicrobial liquid oral medication long-term. Caries Res 1996;30:16-21.
Jain HH, Nanjundaiah V, Hiremath S, Nagesh C, Jacob J, Prasad K. Knowledge and attitudes of pharmacists regarding sugar content in medicine in Bangalore city: A questionnaire study. J Indian Assoc Public Health Dent 2016;14:318-22. [Full text]
Nikiforuk G. Understanding Dental Caries. Basel: Karger; 1985. p. 150.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]