|Year : 2015 | Volume
| Issue : 2 | Page : 143-146
An in vitro analysis of the cariogenic and erosive potential of pediatric liquid analgesics
Shaam Saeed1, Nada Bshara1, Juliana Trak2, Ghiath Mahmoud3
1 Department of Pediatric Dentistry, School of Dentistry, Damascus University, Damascus, Syria
2 Department of Analytical and Food Chemistry, School of Pharmacy, Damascus University, Damascus, Syria
3 Department of Orthodontics and Orofacial Orthopedics, Damascus University, Damascus, Syria
|Date of Web Publication||15-Apr-2015|
Dr. Shaam Saeed
Department of Pediatric Dentistry, School of Dentistry, Damascus University, Mazze Highway, Damascus
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Analgesics such as Ibuprofen and Paracetamol, which are clinically used for the treatment of fever and/or pain, are among the most frequently used pediatric medicines. However, the properties of these preparations determine their cariogenic and erosive potential. Aims: The main objective of this study was to analyze the pH, viscosity and total sugar content in a variety of Syrian pediatric liquid analgesics (PLA). Setting and Design: A total of 16 available liquid analgesics that belong to the Paracetamol and Ibuprofen group were analysed. Materials and Methods: The endogenous pH was measured using a digital pH meter, the viscosity was measured using a digital rotational viscometer and the total sugar content was performed according to Fehling method. Statistical Analysis: Data were presented by means of descriptive statistics (mean, standard deviation, minimum and maximum values). Results: The mean endogenous pH of PLA was 4.63 ± 0.57 ranging between 3.93 and 5.68, and almost all of analgesics (93.8%) had pH values ≤5.5. The mean viscosity of PLA was 243.56 ± 186.6 cP and varied between 20.5 cP and 640.5 cP. Sugars were detected in 11 (68.75%) analgesics, and varied considerably among sugar-containing analgesics from 5.38 to 69.4 (g/100 mL) with a mean concentration of 24.97 ± 23.24 g/100 mL. Conclusion: PLA are potentially cariogenic and erosive because of low pH, high viscosity and high total sugar content. This may increase our concerns about the dental health of children who take liquid analgesics frequently or when long-term treatment is indicated.
Keywords: Dental caries, erosion, liquid analgesics, pH, total sugar content, viscosity
|How to cite this article:|
Saeed S, Bshara N, Trak J, Mahmoud G. An in vitro analysis of the cariogenic and erosive potential of pediatric liquid analgesics. J Indian Soc Pedod Prev Dent 2015;33:143-6
|How to cite this URL:|
Saeed S, Bshara N, Trak J, Mahmoud G. An in vitro analysis of the cariogenic and erosive potential of pediatric liquid analgesics. J Indian Soc Pedod Prev Dent [serial online] 2015 [cited 2021 May 18];33:143-6. Available from: https://www.jisppd.com/text.asp?2015/33/2/143/155129
| Introduction|| |
Pediatric liquid analgesics (PLA) are widely prescribed and are easily accepted by both parents and children.  However, these drugs can place patients at risk for dental caries and dental erosion, especially when used on a regular basis and over a long period of time. 
Sucrose is widely used in the pharmaceutical industry due to its properties as preservative, antioxidant, solvent and thickening agent. It is also a low-cost, easily processed and pleasantly sweetish substance. , However, frequent ingestion of sugars can be rapidly fermented by oral bacteria producing sufficient acid to dissolve dental enamel. 
Acids are commonly used in medicines as buffering agents to maintain chemical stability, control tonicity or to ensure physiological compatibility. In addition, acids are used to improve flavor as well as promote the acid-base reactions that act to disperse effervescent and dispersible tablets on contact with water.  However, when these medicines' pH is below 5.5, they may activate dental erosion. 
This problem especially concerns chronically sick children who require long-term medication, and children who receive medications frequently because of various recurrent benign pathologies, such as coughs and colds. , Although a public-health policy to limit sugar in medicines has been implemented in several developed countries, some developing countries do not have a policy for the use of pediatric medicines especially because of the lack of information on their sugar content and acidity.  As per our knowledge, there is no information about the properties of Syrian PLA. Therefore, the aim of the present study was to analyze the endogenous pH, viscosity and total sugar content in these medicines.
| Materials and Methods|| |
The study was conducted on 16 PLA - which belong to both the Paracetamol and Ibuprofen group - with different brand names and pharmaceutical manufacturers. Samples of medicines were collected from the Central Pharmacy of Damascus and several local pharmacies. The determination of pH and viscosity of medicines was performed at the laboratory of physical analysis at the directorate of pharmaceutical control and research laboratories in Damascus, and the determination of total sugar content was made at the laboratory of chemistry at the school of dentistry, Damascus University, Syria under the following steps:
Endogenous pH 
The pH of each medicine was determined using a digital pH meter (GLP 22, Crison Instruments, SA, Spain). The pH meter accurate to 0.01 was first calibrated. As much as 25 mL of each medicine was placed in a beaker, the electrode was immersed and then the value was recorded. All the readings were taken at room temperature and performed in triplicate.
The viscosity was measured in centipoises (cP) using a calibrated digital rotational viscometer (Visco Star Plus, Funjilab, Spain). A suitable spindle was chosen and the speed of the spindle (rpm) was adjusted, so the percentage of full scale was between 15-95%.
Total sugar content
The determination of the total sugar content was made by the volumetric method (Fehling) that is adopted at the School of Pharmacy at Damascus University, Damascus, Syria. Initially, it was made by the inversion of non-reducing sugars (sucrose) by acid hydrolysis. Five milliliters of medicine were measured by a pycnometer, diluted to a volume of 50 mL with distilled water. Then, 5 mL of hydrochloric acid (HCl 60%) was added to the solution, and the volume was made up to 100 mL. The diluted solution contained in a flask was heated to 70°C and kept in water bath for 10 minutes in order to obtain glucose and fructose molecules. The mixture was cooled immediately in cold water, had its pH neutralized by titrating with 20% NaOH, and the neutral solution was diluted to a final volume of 200 mL. For titration, 5 mL of solution A and 5 mL of solution B of the Fehling reagents, 5 mL of 15% ferrocyanide potassium, and 10 mL of distilled water were mixed in a conical flask and put on a burner to boil gently. The Fehling solution was first standardized with a standard invert sugar 2.5%, and the volume needed to change the color of Fehling solution from blue to green to yellow, then brown - due to the presence of ferrocyanide potassium - as an indicator of the turning point was recorded. The neutralized diluted medicine was transferred to a 25-mL burette, added gradually to Fehling solution, and the volume required for titration was recorded. Total sugars present in the sample were calculated according to the following equation:
Data were organized with the aid of the Statistical Package for Social Sciences (SPSS) version 13 and presented by means of descriptive statistics (mean, standard deviation, minimum and maximum values).
[Table 1] shows endogenous pH, viscosity values and total sugar content of PLA.
|Table 1: Means and standard deviations for Endogenous pH, viscosity values and total sugar content of pediatric liquid analgesics|
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Most PLA were acidic with pH values ranging between 3.93 and 5.68, and a mean of 4.63 ± 0.57. Almost all of analgesics (93.8%) had pH values ≤5.5 for enamel demineralization, while only one medicine had a pH >5.5. Viscosity values of PLA ranged between 20.5 cP and 640.5 cP with a mean of 243.56 ± 186.6 cP. Regarding the total sugar content, sugars (reducing and non-reducing sugars) were detected in 11 (68.75%) analgesics, while only 5 PLA were sugar-free. Total sugar content varied considerably among sugar-containing analgesics from 5.38 to 69.4 (g/100 mL) with a mean concentration of 24.97 ± 23.24 (g/100 mL) [Table 1].
| Discussion|| |
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. 
Regular use of sugar-containing liquid medicines is often implicated in the development of dental caries in children.  Children on an average take medicine every eight hours daily or 10 times a week. Moreover, other healthy children who take medicines infrequently and for short periods are also at risk. 
Our study showed that almost all of PLA had pH values ≤5.5 for enamel demineralization with pH values ranging between 3.93 and 5.68. A pH of 5.5 is traditionally considered to be the 'critical pH' for enamel dissolution although mineral loss may begin at higher pHs. 
This result is in accordance with several studies showing that most pediatric liquid medicaments were acidic. ,,,,, Passos et al.,  and Xavier et al.  found that 44% and 56% of pediatric liquid medicines had pH values below 5.5, respectively, while other studies sated that 70%,  80%,  87%  and 90%  of analyzed medicines were below this value. The mean pH in our study was 4.63 ± 0.57, which was lower than in other studies. ,, Therefore, children frequently taking these acidic medicines are at potential risk of developing dental erosion.  However, the erosive potential of food of liquid preparations also depends on pH, titratable acid, type of acid (pKa), calcium chelation properties and physical and chemical properties affecting adherence to the enamel surface and stimulation of salivary flow.  Since tooth brushing is not suggested soon after acid medication ingestion, caries risk in these cases is also high. 
The present study showed that viscosity values ranged between 20.5 cP and 640.5 cP. Subramaniam et al.  found that viscosity of pediatric liquid medicines varied from 307.33 cP to 2408.3 cP, and ranged in Neves et al.  study between 2.8 cP and 412.3 cP.
Liquid oral medicines are usually viscous syrups that penetrate into fissures and proximal areas that are inaccessible to the toothbrush. Therefore, regular and long-term use of medications with prolonged oral clearance may increase the risk of dental caries if they contain sugars or dental erosion if they contain acids. Therefore, children should also be encouraged to rinse their mouths with water after taking such medicines. 
Most PLA evaluated contained sugar supporting previous findings that have shown that 50-71.43% of liquid medicines had sugar. ,,,,, However, Cavalcanti et al.  found that only 33% of medicines analyzed had sugar. It is well-known that sugar-rich medicines cause in vivo drop in pH of the dental plaque.  On the other hand, poly-alcohols such as sorbitol and xylitol are important sugar substitutes since they are not efficient substrates for plaque bacteria and therefore produce only a minimal plaque pH drop. 
Total sugar content varied considerably among sugar-containing analgesics from 5.38-69.4 (g/100 mL), which is in accordance with previous studies that have shown a wide range in sugar content of pediatric syrups from 7.31-85.9%. ,,,, As the sucrose concentration solution to form the cariogenic biofilm is 5%, it can be argued that all sweetened analgesics analyzed have the potential to provide conditions satisfactory to dental carious lesions. Nevertheless, the cariogenic potential of any medicine must take into account not only its sucrose concentration; but also its frequency of use, dose and pattern of use.  Many preventive measures have been suggested such as brushing teeth after taking each dose, but not immediately after an erosive challenge, taking medicines at meal times rather than between meals, avoiding the intake of medicines at bedtime, chewing sugarless gum to stimulate the secretion of saliva, topical fluoride applications and regular preventive dental care. , However, as many children do not brush their teeth after the intake of medicines, a practical and effective way of preventing dental caries caused by medicines is to use a sugar-free preparation  or replace syrups and suspensions with tablets whenever possible especially among older children on long-term medication.
This study highlights the need to influence pharmaceutical industries to reformulate sugar-free liquid analgesics with low acid levels, low viscosity and reasonable prices as it is preferred for long-term treatment.
On the other hand, parents of young children who consume liquid oral analgesics, pharmacists who guide consumers and physicians that prescribe pediatric syrups would be the obvious targets for campaigns to encourage the change to sugar-free analgesics.  Moreover, pediatric dentists should take the responsibility of informing pediatricians about the profile of the routinely prescribed analgesics  to put in practice oral health instructions for their patients.
In addition, Syrian Pharmaceutical Association has the responsibility to pressure manufacturers to produce all PLA in sugared and non-sugared forms.
| Conclusion|| |
In summary, our data showed that most PLA tested had pH values below the critical value, high viscosity and high total sugar content all of which increase the medicines' cariogenic and erosive potential. Caution about dental caries and dental erosion is warranted, and sugar-free medicines should be promoted among children when long-term treatment is indicated.
| References|| |
Subramaniam P, Nandan N. Cariogenic potential of pediatric liquid medicaments-an in vitro Study. J Clin Pediatr Dent 2012;36:357-62.
Arora R, Mukherjee U, Arora V. Erosive potential of sugar free and sugar containing pediatric medicines given regularly and long term to children. Indian J Pediatr 2012;79:759-63.
Cavalcanti AL, de Oliveira KF, Xavier AF, Pinto DS, Vieira FF. Evaluation of total soluble solids content (TSSC) and endogenous pH in antimicrobials of pediatric use. Indian J Dent Res 2013;24:498-501.
Pomarico L, Czauski G, Portela MB, de Souza IP, Kneipp L, de Araújo Soares RM, et al
. Cariogenic and erosive potential of the medication used by HIV infected children: pH and sugar concentration. Community Dent Health 2008;25:170-2.
Mayo JA, Ritchie JR. Acidogenic potential of "sugar-free" cough drops. Open Dent J 2009;3:26-30.
Maguire A, Baqir W, Nunn JH. Are sugars-free medicines more erosive than sugars-containing medicines? An in vitro study of paediatric medicines with prolonged oral clearance used regularly and long-term by children. Int J Paediatr Dent 2007;17:231-8.
Neves BG, Farah A, Lucas E, de Souza VP, Maia LC. Are paediatric medicines risk factors for dental caries and dental erosion? Community Dent Health 2010;27:46-51.
Soares DN, Valinoti AC, Pierro VS, Antonio AG, Maia LC. Cross-sectional microhardness of bovine enamel subjected to three paediatric liquid oral medicines: An in vitro study. Eur Arch Paediatr Dent 2012;13:261-5.
Sunitha S, Prashanth GM, Shanmukhappa, Chandu GN, Subba Reddy VV. An analysis of concentration of sucrose, endogenous pH, and alteration in the plaque pH on consumption of commonly used liquid pediatric medicines. J Indian Soc Pedod Prev Dent 2009;27:44-8.
Cavalcanti AL, Fernandes LV, Barbosa AS, Vieira FF. pH, titratable acidity and total soluble solid content of pediatric antitussive medicines. Acta Stomatol Croat 2008;42:164-70.
De Almeida LF, Abílio GM, Cavalcante MT, Castro RD, Cavalcanti AL. Cariogenic and erosive potential of industrialized fruit juices available in Brazil. Braz J Oral Sci 2010;9:351-7.
Cavalcanti AL, Sousa RIM, Clementino MA, Vieira FF, Cavalcanti CL, Xavier AF. In vitro analysis of the cariogenic and erosive potential of paediatric antitussive liquid oral medications. Tanz J Health Res 2012;14:1-8.
Agrawal N, Shashikiran ND, Vanka A, Thakur R, Sandhu SS. Cariogenic potential of most commonly prescribed liquid oral medicines for children. People's J Sci Res 2010;3:7-10.
Xavier AF, Moura1 EF, Azevedo WF, Vieira FF, Abreu MH, Cavalcanti AL. Erosive and cariogenicity potential of pediatric drugs: Study of physicochemical parameters. BMC Oral Health 2013;13:71.
Passos IA, Sampaio FC, Martínez CR, Freitas CH. Sucrose concentration and pH in liquid oral pediatric medicines of long-term use for children. Rev Panam Salud Publica 2010;27:132-7.
Babu KL, Rai K, Hegde AM. pH of medicated syrups-does it really matter?-an in vitro study: Part-II. J Clin Pediatr Dent 2008;33:137-42.
Peres KG, Oliveira CT, Peres MA, Raymundo Mdos S, Fett R. Sugar content in liquid oral medicines for children. Rev Saude Publica 2005;39:486-9.
Rekola M. In vivo acid production from medicines in syrup form. Caries Res 1989;23:412-6.