|Year : 2021 | Volume
| Issue : 1 | Page : 158-165
Evaluation of erosive and cariogenic potential of pediatric liquid formulated drugs commonly prescribed in India: A physiochemical study
Anshula Neeraj Deshpande, Neha Pradhan, KS Poonacha, Bhavna Dave, Rameshwari Raol, Aishwarya Jain
Department of Pediatric and Preventive Dentistry, K.M. Shah Dental College and Hospital, Sumandeep Vidhyapeeth, Vadodara, Gujarat, India
|Date of Submission||06-Jul-2020|
|Date of Decision||03-Nov-2020|
|Date of Acceptance||28-Dec-2020|
|Date of Web Publication||29-Jul-2021|
Dr. Anshula Neeraj Deshpande
Department of Pediatric and Preventive Dentistry, K.M. Shah Dental College and Hospital, Sumandeep Vidhyapeeth, Vadodara, Gujarat
Source of Support: None, Conflict of Interest: None
Context: Many children receive medications for recurrent acute illness and vitamin supplements prescribed by a pediatrician. These medications for young children are in form of syrup and emulsion which are of high sugar content and low pH. These medications make teeth susceptible tooth erosion. Aim: The aim was to evaluate the erosive and cariogenic potential of mid cariogenic potential of pediatric drugs prescribed in India by physicochemical methods. Materials and Methods: The drugs used in this study compromised 96 liquid drug preparations commercially available as oral solution, suspension, elixir, syrup, and drops commonly prescribed for various ailments for children. Tests were performed in triplicate by a calibrated researcher. The endogenous pH of each sample was determined using digital pH meter HI-253. The measurements of the total soluble solids contents were done using the method proposed by the Ayurvedic Formulary of India and the sugar content was determined according to the prescription. Descriptive statistics were employed to compare the results. Results: All drug classes showed acidic pH, and the lowest mean was found for anticonvulsants (4.2 ± 0.20). The variation in the total titratable acidity was from 0.0% to 0.03% among all the drug classes. The highest TSS values were found in bronchodilators 52.75 ± 14.32. Almost all the syrups failed to mention syrup base in their content. Conclusion: It was found that sugar is present in almost all the commercially available pediatric syrups, and a lot of the syrups have their pH close to the critical pH of teeth.
Keywords: Cariogenic, children, erosive potential, liquid formulation, pediatric drugs
|How to cite this article:|
Deshpande AN, Pradhan N, Poonacha K S, Dave B, Raol R, Jain A. Evaluation of erosive and cariogenic potential of pediatric liquid formulated drugs commonly prescribed in India: A physiochemical study. J Datta Meghe Inst Med Sci Univ 2021;16:158-65
|How to cite this URL:|
Deshpande AN, Pradhan N, Poonacha K S, Dave B, Raol R, Jain A. Evaluation of erosive and cariogenic potential of pediatric liquid formulated drugs commonly prescribed in India: A physiochemical study. J Datta Meghe Inst Med Sci Univ [serial online] 2021 [cited 2021 Sep 16];16:158-65. Available from: http://www.journaldmims.com/text.asp?2021/16/1/158/322619
| Introduction|| |
Dental hygiene is an essential part for well-being, growth, and development of an infant. Dental caries is the most common disease affecting the oral cavity. The most common attributable cause is the bacterial fermentation of the acid-producing carbohydrates in the diet which in effect erodes the tooth. Including diet, it is often assumed that other drugs accentuate tooth degradation. Considering the advancements, we have made so far in the field of preventive dentistry, it remains a daunting challenge to prevent and handle dental caries among children. It has been a well-established fact that the nature, concentration, and frequency of sugar consumption in different forms and dental caries are directly related.
Although parents are well aware of the fact that sugar causes tooth decay, they believe that confectionaries and soft drinks are the only potential sources of high sugar content and are unaware of the fact that routinely administered medicines can also be a source of sugar. Systemic drug administration includes routes to oral, sublingual, rectal, cutaneous, inhalation, nasal, and parental. Among these routes, the oral route is the most popular and oldest mode of drug administration in the pediatric age. Pediatric liquid preparations are popular with both parents and children and are easily embraced.
In pediatric medicine, syrups have a long history of use. These are widely prescribed and easily accepted by children. Their usage is typically for a short time, but it may be a regular occurrence for some children. If such liquid formulations are given over long period of time, there is an increased risk of developing dental caries. Children undergoing medication for chronic conditions such as severe respiratory infections, asthma, epilepsy, heart disease, renal failure or tumors, and recurring acute diseases such as tonsillitis, otitis, sinusitis, or even vitamin supplements or iron tonics are also vulnerable to developing dental caries.,
The Caries risk assessment tool (CAT) for AAPD caries stipulates that children with chronic illnesses may be at higher risk for dental disease. Cavalcanti et al. in 2012 stated that the pediatric antitussives are potentially cariogenic and erosive to the tooth structure and Arora et al. in 2012 observed that pediatric sugar-free medicines were less erosive than sugar containing medicines.
Different physiochemical properties of medicines were studied and the pH, total titratable acidity (TTA), total soluble content, and sugar content, respectively, were found to be responsible for the erosive and cariogenic potential., Clear comparative studies indicate the high incidence of caries in children who use prescription products containing long-term sugar than those who are not on medication.
Tooth dissolution is the loss of tooth substance due to chemical processes that do not involve bacteria; this is due to the acid that acts both intrinsically and extrinsically on a susceptible tooth. The amount of acid available (titratable acidity), the amount of acid present (pH), and the acid intensity (pKa) are the properties that contribute to the acid's erosive potential. Acidic preparations are used in drug dispersion or in effervescent tablets to facilitate the acid–base reaction, and long-term use of this acidic preparation can result in tooth dissolution.
Although the active ingredients in the medical formulations are essential for treatment, it is the inactive ingredients and additives that cause other problems that can be prevented, such as dental erosion. This growing concern among pediatric dentist about intake of liquid medications containing sugars has increased. There are very few studies that measure the erosive and cariogenic potential of pediatric drugs, we aimed to assess the erosive and cariogenic potential of widely prescribed liquid pediatric drug formulations through physiochemical quantitative analysis of pH, TTA, total soluble content, and content of sugars.
| Materials and Methods|| |
The present research project was an in vitro study which was initiated after obtaining approval from the ethical committee of the institute. This study was conducted at dental college in the Department of Paedodontics and Preventive Dentistry with technical expertise provided by the College of Pharmacy of the same university. This research was performed on a total of 96 medications grouped into 7 classes including antibiotics, analgesics and antipyretics, antispasmodics, cough and cold medicines, bronchodilators, anticonsultants, and dietary supplements as shown in [Table 1],[Table 2],[Table 3],[Table 4],[Table 5]. The study included pediatric drugs prescribed for a minimum duration of 3 days or more consecutively, and drugs not approved by the CDSCO or not prescribed in India were exempted from the study. A properly calibrated researcher tested triplicate. The intraclass coefficients were calculated by comparing TTA and total soluble solids content (TSSC) scales, and the calibrated researcher reported the readings.
|Table 2: List of pediatric drugs in class of analgesics and antipyretics and antispasmodics|
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|Table 3: List of pediatric drugs in class of cough and cold preparations|
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|Table 4: List of pediatric drugs in class of bronchodilators and anticonvulsants|
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Digital pH meter HI-253 (Systronics Ltd, Ahmedabad, Gujarat, India) estimated the endogenous pH of each sample. Initially, samples were diluted in distilled water so that 10 mL of each medicine was transferred to a 100-mL volumetric flask and the total volume was achieved by adding 90 mL of distilled water. Out of 100 mL, 50 mL of the mixture was transferred to a beaker and a glass electrode was immersed therein, and values were recorded [Figure 1].
Analysis of total titratable acidity
To investigate TTA, measured by acid percentage, 50 mL of the diluted solution was used, maintained under constant stirring using a magnetic stirrer. The pH meter electrode was immersed in this diluted solution while a 0.1 N sodium hydroxide (NaOH) solution was titrated until the pH dropped to 8.2-8.4, corresponding to the phenolphthalein turning point (acid–base indicator that changes color in well-defined pH values) [Figure 2]. The NaOH volume was then used to record the acid percentage of the substance using the chemical formula described below, which was adjusted due to the dilution process and expressed as a percentage of citric acid.
V = NaOH volume
Nap = standard concentration of the potassium hydroxide base;
F = correction factor;
meq-g = milliequivalents per gram of citric acid;
Sample = drug volume.
Analysis of total soluble solids content
The measurements of the TSSC were done using the method proposed by the Ayurvedic Formulary of India; we transferred 50 ml of clear syrup in an evaporable dish and evaporated it to a thick extract on a water bath [Figure 3]. Unless specified otherwise, the residue was extracted with 4 quantities, each of 10 ml, of dehydrated ethanol with stirring and filter. The filtrates were combined to another evaporating dish which was dried to a constant weight and evaporated nearly to dryness of water bath. After this 1 g of diatomite (dried at 105° for 3 h and cooled in a desiccator for 30 min), was stirred in thoroughly and dried at 105° for 3 h and the dish was cooled in the desiccator for 30 min and weighed immediately [Figure 4]. Deducting the weight of diatomite added, the weight of the residue gave the weight of the TSSC.
|Figure 3: Syrup transferred to evaporable dish to analyze total soluble solids contents|
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|Figure 4: Filtrate transferred to desiccator to analyze total soluble solids contents|
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Measurement of sugar content
The sugar content was calculated by analyzing the content sticker given on the medicines. In addition to this information on the type of acid and sweetener contained in the formulations, the medicine package inserts gathered [Figure 5].
Data were recorded on study-specific charts and organized with the aid of the SPSS version 21 (Statistical Package for the Social Sciences, IBM Corporation, USA) and presented by means of descriptive statistics (mean, standard deviation, and minimum and maximum values). Unpaired t-test and Chi-square test were used to analyze the data for various variables.
The study was conducted after obtaining ethical clearance from Sumandeep Vidyapeeth Institutional Ethics Committee (SVIEC) Ref no : SVIEC/ON/DENT/SRP/76247.
| Results|| |
All of the drugs included in the study were checked for acidic pH, TTA, TSSC, and sugar content. Among the 7 categories of drugs that underwent analysis, only nutritional supplements disclosed of having sucrose in it. Four out of 15 nutritional supplements had sucrose content in them with a mean value of 29.75%; this accounts for 26.7% of all nutritional supplements subjected for analysis and 4.2% of the total 96 drugs analyzed. There was great variability within each category of drugs with antibiotics, analgesics, antispasmodic, and nutritional supplements showing acidic and basic pH within the group among which nutritional supplements showed the greatest standard deviation of 1.084 [Table 6]. In the following table, all 7 classes of drugs showed a significant difference in the values of TTA, where it was least for antispasmodic with a mean value of 0.01 mmol and highest for anticonvulsants with a value of 0.03 mmol [Table 6].
|Table 6: Descriptive statistics of recorded pH, total titratable acidity, and total soluble solute content in all 7 classes of drugs|
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Acidic pH was recorded in most of the antibiotics, analgesics, and antipyretics, cough and cold preparations, bronchodilators, and anticonvulsants with mean pH values of 5.6, 6.1, 5.7, 5.5, and 4.4, respectively, while basic pH was recorded in most antispasmodics and nutritional supplements with mean pH values of 7.1 and 7.2, respectively, as shown in [Figure 6].
The variations were also marked for few classes of drugs when total soluble solvent was concerned. The total soluble solute was highest in bronchodilators (52.75%) and least in antibiotics (33.15%) [Figure 7].
| Discussion|| |
Various clinical and in vitro studies have highlighted a growing awareness of the cariogenic potential of liquid oral medicine formulations in the pediatric age group. The free access of counter medicinal products masks the true use of medicinal products in children. Although studies on long-term medication show definite risk in the development of dental caries and tooth erosion in children, there are only a handful of studies that quantitatively evaluate pharmacological agents' physiochemical properties.
Erosive potential of liquid formulated pediatric drugs
The erosive potential was evaluated by pH analysis, which showed that the majority of the liquid formulations being used are acidic in nature and certain antibiotics and anticonvulsants have recorded pH values of 4.6 and 4.21, respectively, which are significantly below the critical value of 5.5. Although the mean pH value for all categories of drugs except anticonvulsants is above 5.5 (4.48), the great variation within each group is evident as the standard deviation is high (0.2–1.08) which shows the amount of drugs dropping below the critical pH value for erosive potential on tooth enamel. This is consistent with prior studies by Passos et al. and Xavier et al. which reported 44% and 56% of pediatric liquid medicinal products having pH values below 5.5., It is noteworthy that citric acid is used in most of liquid preparations. Due to strong chelating properties of citric acid it is known to produce high levels of erosion. Cavalcanti et al. in 2012 also concluded that the pediatric antitussive medications showed pH below the critical value. Results from present studies showed that few drugs alkaline in nature in the class of analgesic are Crocin DS 250 mg with pH of 7.39, Calpol DS 250 mg with pH of 7.54, and Mefkind-P with pH of 7.2; in antibiotics, it is Novamox 250 mg with pH of 7.42 and in nutritional supplements, they are Ostocalcium with pH of 7.31, Ostopolybion D with pH of 8.1, Tonoferon paediatric with pH of 7.79, and iron and calcium supplements.
The other parameter that was evaluated for erosive potential was TTA which, in turn, shows the strength of the erosive potential and the values varied between 0.1 and 0.03 which was a contradictory finding as compared to previous studies that showed high TTA in many liquid medications., Neves et al. in 2010 stated that high titratable acidity values increase cariogenic and erosive potentials of medications. Yılmaz et al. in 2019 concluded that commonly used and prescribed pediatric drugs risk tooth erosion. The effect of few drugs prescribed by pediatric dentists causes erosion and they should stress on compliance with oral hygiene procedures.
Cariogenic potential of liquid formulated pediatric drugs
The cariogenic effect of drugs was also evaluated, here researchers found surprising results when examining the sugar content given on the drug's content sticker, that only four drugs displayed exactly the same sugar content as that on the content sticker. Those four medications belonged to the nutritional supplement category. When taken regularly by pediatric patients, having medications with a higher sugar content can cause severe dental caries. Maguire et al. in 2007 concluded that sugar-free medicines were not more erosive than sugar containing medicines. Pharmaceutical companies sweeten liquid drug preparation with sugars such as sucrose, fructose, and glucose to enhance palatability, add bulk, and supposedly enhance compliance. Sucrose continues to be widely used as it is cheap, nonhygroscopic, and easy to process., According to Pomarico et al. in 2008, antibacterial contained the highest concentration of sucrose, from 40% to 54%. Glucose was found in one of the ten, sucrose was present in seven of them, and none of them contained lactose. Children with HIV infection are at significant risk of caries and dental erosion.
The total soluble solute is a measure of the amount of solid material in the formulation which, in turn, has a direct relationship with the viscosity. Viscous syrups are known to penetrate the fissures and to areas inaccessible to toothbrush. The soluble solute content showed values as high as 76% in a drug and the mean values 33.15%–52.75%. This goes tandem with various other studies that measured viscosity or total soluble solute content. Neves et al. viscosity values varied between 2.8 cP and 412.3 cP. High titratable acidity values increase cariogenic and erosive potentials of medications. Subramaniam and Nandan antitussive and nutritional supplement showed the highest TSSC. The physical properties and concentration of sugars in them may indicate their cariogenic potential. Siddiq et al. in 2020 quoted that the pediatric LOMs revealed sugar content, low endogenous pH, high titratable acidity, and high total soluble solids.
The constant pressure by the pediatric and preventive dentist armed with published data has forced pharmacological companies to decrease the indiscriminate use of additives in pediatric liquid formulations. A total cessation of the use of liquid medication in the pediatric age group is not possible, but awareness about the potential hazards in the dental hygiene of children taking long-term medication should be imparted to the parents who would, in turn, take necessary action like proper oral irrigation after administration of drugs, especially during bedtime and inadvertent over the counter nutritional supplement usage would decline.
| Conclusion|| |
Children those who are routinely subjected to drugs, proper oral hygiene should be governed by parents for them. There were few drugs in each category which were basic in nature and can be prescribed, e.g., (1) in analgesics – Crocin DS 250 mg, Calpol DS 250 mg, and Mefkind-P; (2) antibiotics – Novamox 250 mg; (3) nutritional supplement – Ostocalcium, Ostopolybion D, and Tonoferon pediatric. Iron and calcium supplements were also basic in nature. There were only four drugs which showed exact sugar content as that on the sticker; they were Neurogen, Zincovit, A to Z, and Mulmin. Investigators concluded that all the pharmaceutical companies should mention statement like -”To prevent tooth decay maintain oral hygiene” on bottles as caution as well as advisory should be sent to use FDA approved sugar sweeteners.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]