Influence of Different Beverages on Disintegration Behavior of Pain Reliever Immediate Release Formulations

 

Hardik B. Rana*, Kajol Patel, Mansi Dholakia, Vaishali T. Thakkar, Mukesh C. Gohel, Tejal R. Gandhi

Department of Pharmaceutics, Anand Pharmacy College, Anand - 388 001, Gujarat, India

 

 

ABSTRACT:

The objective of the present study was to assess the influence of different beverages like Coco-cola, Orange juice, butter milk, 6% fat and 5% fat containing milk on three immediate release pain reliever tablets of Nimesulide, Mefanamic acid and Aceclofenac. The study was performed in USP disintegration apparatus using different gastric simulated media at 37±0.5 ºC. A hybrid medium of different beverages (640 ml) with 0.1 N HCl (140 ml) was prepared to mimic in vivo condition. The result shown that disintegration time was increased in milk, buttermilk and orange juice and decreased in Coca cola compared to 0.1 N HCl. As the viscosity of fluid increses, the disintegration time was also increased. Coco-cola which contains Carbon Dioxide which was reduce the disintegration time of formulation. From the above study it can be concluded that there is variation in disintegration time of different formulations in different beverages. The patient on these medications should be advised against consuming different beverages with medications because it will affect bioavailability of mediation.

 

 

 

INTRODUCTION:

Oral solid dosage forms such as tablets and hard-gelatin capsules, which have been in existence since the nineteenth century, remain the most frequently used dosage forms today. Tablets and capsules accounted for about half of the 579 new medicines licensed from 1995 to 1999 (221 were in tablet dosage form and 51 in capsule form) ¹. A tablet that can withstand the stresses of subsequent packaging operations and reach the patient in an acceptable condition is generally assessed by friability and hardness tests.

 

Disintegration is an important physical property of a tablet dosage form during the research and development stage and is most commonly studied in either water or simulated gastric medium and occasionally in simulated intestinal medium. However, patients do take medications with beverages other than water. Often patients are counseled to take medications, especially pain-relief medications, with milk to decrease the potential for gastric irritation.

 

Disintegration can simply be defined as the process of breaking up of solid materials when in contact with a liquid medium. This usually involves the breaking of internal bonds of the solid material. Tablet disintegration is the disruption of internal bonds and a subsequent breakdown of tablets into granules as a result of the penetration of the tablets by an aqueous medium. The availability of a drug from a tablet depends on the tablet’s ability to disintegrate fast enough in existing dissolution media.² Therefore, disintegration is the prerequisite for dissolution of active drug after oral administration of solid dosage forms. The disintegration time is often used to determine whether tablets or capsules would disintegrate within the desired time when placed in a liquid medium at given experimental conditions.^3,4 This test is a useful tool for quality control and can be a critical parameter for drug release in certain scenarios like highly soluble drugs. ^{5, 6} Several studies have shown that the presence of food in the stomach delays or retards disintegration times of drugs.^{7, 8} Zuo et al and Sreelesh et al studied the effect of some beverages on the disintegration time of four dietary supplements and three pain-relief tablets respectively and they observed that the disintegration times of the tablets were delayed by the beverages and in some cases quite significantly. ^{9, 10}

 

It is well established that drugs should be taken with a glass of water, while many dietary supplements do not give any further instructions except for the units per serving. No beverage (e.g., water) is specified, and it can be assumed that any available beverage, including pop, juices, and alcoholic beverages, might be used for the administration of dietary supplement dosage forms.⁷

 

Recent advances in pharmaceutical technologies, polymer sciences and analytical tools have enabled design of smarter drug delivery systems. Various formulation strategies are employed for optimizing the therapeutic efficiency and/or minimizing side effects of drugs designed as smart dosage forms. Such techniques used for extended release or programmed release or targeted release has generated many patents. They not only offer the manufacturers an edge above the competitors but often offer obvious advantages to the patients also due to reduced dose frequency, reduced total dose consumption and minimal exposure of the non-target tissues to pharmacological effects. Most of the patients traditionally consume the medicines with one or more of the beverages including the health drinks with complex compositions. It is known fact that there is a great variation in the quantity and the regimen followed for consumption of these beverages. Here are possibilities of probable interactions between any of the components of these beverages and the formulation ingredient including the drug candidate. Such interactions have so far been neglected and only a few like those with the grapefruit juice have been reported. A few reports also cite the dramatic alterations in the release profiles of commonly used OTC type drugs due to concomitant consumption of alcoholic beverages. Unlike the drug-drug or food drug interactions however, the data available on probable drug –beverage interactions is very limited. Classically any of the interactions can be classified as   follows; Drug-Drug Drug –Food Drug- Chemical Drug- Disease the net effect of any type of drug interaction is generally, Quantitative i.e. increased or decreased therapeutic response Rapid or slower effect Precipitation of newer or increased adverse-effects.¹¹

 

Most of these adverse reactions alter the efficacy of drug e.g. Tetracycline when concomitantly administered with food, antacid or mineral supplements containing metal ions. Moreover, such adverse interactions may offset the advantages of drug delivery from specially designed formulations which act as smart delivery systems. Hence, there is great need to explore the possible drug-beverage interactions and develop tools to elucidate their probable mechanisms. Such data would help to redefine the formulation strategies for conventional and/or novel drug delivery systems and recommend altogether new dose regimens for the patients. A screening is also needed to know more details about the composition of beverages including   various   food   drinks,   social drinks which are consumed routinely.¹² The Indian population generally consumed food drinks, social   drinks.   The   most   common beverages consumed by Indian population include; Tea, Coffee, Buttermilk, Aerited, non- Aerited etc. These beverages are consumed on large scale and people are yet to be aware of the possible interaction of these beverages with commonly used drugs which are available as over the counter (OTC) product viz. such as analgesic, anti- inflammatory agent etc. This work aims to focus on major issues of altered release or absorption pattern of some drugs that can be improved by minimizing side effect.¹³

 

MATERIALS AND METHODS:

Materials:

Hydrochloric acid (36.5–38.0%) was purchased from Dutt Chemicals Pvt. Ltd., Anand.

 

Commercial Tablet Model Dosage Forms:

Three IR pain-relief tablets were chosen as study products. Mefenamic acid 250mg tablet (Blue cross laboratories Ltd, batch No. HMT 1419, Exp. August 2017). Nimesulide 100 mg tablet (Dr. Reddy’s Laboratory Ltd., Batch no: E500084, Exp. December 2017). Aceclofeanc 100 mg Tablet (Intas Pharmaceuticals Pvt. Ltd., Batch No.: 1641 Exp. May 2018).

 

Study Media:

Amul Gold (6% Fat), Amul Shakti (4.5% Fat), Butter milk (1.1%), coco-cola (0% fat) were selected as media. Additionally hybrid media were prepared for each of the beverages. Hybrid media were prepared using 160ml 0.1 N HCl and 640 ml different beverages.

 

Methods:

Each of the three study pain medication tablets was dropped into one basket tube of the USP disintegration apparatus (Shimadzu) and loaded into a one-liter, low-form glass beaker filled with 800 mL of media, then lowered into a bath containing 8.5 L of water. The temperature of the bath was maintained at 37.0 ± 0.5 °C throughout the entire test period. The apparatus was calibrated based on the guideline of USP 31–NF 27 to ensure that the basket ascended and descended in an immersion fluid at 29–32 cycles per minute until the tablet was completely disintegrated and fragments fell out of the stainless steel mesh. The disintegration time was then recorded. 0.1 N HCl, Milk, butter milk, orange juice, coco-cola were selected as media.^{14, 15} In addition to this hybrid media was prepares which contains 160 ml 0.1 N HCl and 640 ml different beverages which simulate better in vivo condition.

 

RESULT AND DISCUSSION:

All studied pain-relief tablets showed either similar or delayed disintegration in the test beverages in comparison with 0.1 N HCl. The disintegration time of all there formulation were taken in first 0.1 N HCl (Table 1).

 

 

 

Table 1: Disintegration time of different formulation in 0.1 N HCl

n= 6 tablets of each formulation

 

Effect of Amul Gold and Amul Shakti milk:

Milk is one of the most preferred beverages co- administered with medicines. It is psychological of many patients that co-administration with milk will help reduce the adverse effects of the drugs associated with gastric distress. The disintegration test was performed in hybrid media which contains 160ml 0.1 N HCl and 640ml Amul Gold or Amul Shakti milk and also only in Amul God and Amul Shakti. The result showed six to seven times delayed drug release in all three formulations in pure milk whereas slight lower DT was obtained in Hybrid media in all formulation. In amul gold, the DT was longer as compared to Amul Shakti because Amul Gold contains higher amount of fat. As the fat of milk increases, the DT was also increased. The data of DT in milk for three formulations is shown in Table no. 2. It shows that wide difference should be shown as compare to disintegration time in water all three tablets. The significant delay found in disintegration of medication chosen for study may be due to the lipidic nature of milk and viscosity of milk.

Table 2: Influence of Milk on Disintegration Time

n= 6 tablets of each formulation

 

 

Effect of Amul Masti Buttermilk:

Amul Masti is a well known brand of butter milk which is consumed by many peoples during lunch and dinner. The disintegration test was performed in whole buttermilk and also in  hybrid media which contains 160ml 0.1 N HCl and 640ml Amul masti buttermilk. The DT of all the three formulations indicate longer disintegration time than the 0.1 N HCl but found shorter than milk which is shown in table no. 3. The results shows that vast difference was obtained in buttermilk compared to normal media which suggest again significant results were obtained.

Table 3: Influence of Buttermilk on Disintegration Time

n= 6 tablets of each formulation

 

Effect of Tropicana Juice:

Fruit Juice chosen for this study was orange Juice by Tropicana, a well-known brand for juices. The disintegration test was performed in whole juice and also in hybrid media which contains 160ml 0.1 N HCl and 640ml orange juice to simulate the in vivo condition. The results shown in table no. 4 which indicate longer DT compared to normal media, slight higher to buttermilk than milk.

 

Table 4: Influence of Tropicana Juice on Disintegration Time

n= 6 tablets of each formulation

 

Effect of Coco-cola:

Coco-cola was selected as it was a well known brand of soft drink which contains compressed carbon dioxide. The disintegration test was performed in whole Coco-cola and also in hybrid media which contains 160ml 0.1 N HCl and 640ml Coco-cola to simulate the in vivo condition. The faster disintegration was observed in presence of coco-cola compared to water. Slight higher DT was observed in hybrid media compared to whole coco-cola and lower in comparison with 0.1 N HCl which was shown in Table no. 5. It  may  be suggested that this instant DT may be due to pressure exerted by carbon dioxide gas in sprite irrespective of the drug. Moreover in earlier studies it has been reported that wherever faster disintegration is required, ingredients are chosen which evolve carbon dioxide and break up the tablet. In the experiment, carbon dioxide has some effect on the tablet extremity and thus leads to faster disintegration. Statistical results also indicated that disintegration of all three IR pain relief medications studied gave lower values in regular soft drink than the results obtained in water suggesting faster absorption from GI tract. Due to higher drug release in short time may lead to toxicity or side effect of individual drug. So, administration of Pain reliever medication is avoided with carbonated water.

 

Table 5: Influence of Coco-cola on Disintegration Time

n= 6 tablets of each formulation

 

CONCLUSION:

This study examined the influence of different beverages on the disintegration of three different IR pain relief medications. The study proposed the use of hybrid media which was better simulating the condition of in vivo instead of using blank different beverages. The results above study shown that different beverages affect the disintegration time of different Pain reliever medication. Coco-cola decreases the disintegration time of tablet because of presence of Carbon Dioxide. Other all Medias i.e. Milk, buttermilk and orange juice increases disintegration time because of the presence of fat. As the fat of viscosity of the solution increases, the disintegration time also increases. So, The patient on these medications should be advised against consuming different beverages with medications because it will affect bioavailability of mediation.

 

ACKNOWLEDGEMENT:

The authors are grateful to the authorities of Anand Pharmacy College, Anand for providing the facilities.

 

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

 

REFERENCES

1.       Davies P. Oral Solid Dosage Forms. In Pharmaceutical Preformulation and Formulation. 2nd ed.; Gibson, M., Ed.; CRC Press LLC: Boca Raton, FL, 2004:379.

2.       Ingram JT, Lowenthal W. Mechanism of action of starch as a tablet disintegrant - Factors that affect the swelling of starch grains at 37 °C. J Pharm Sci. 1996; 55(6): 614-617.

3.       Disintegration and Dissolution of Dietary Supplements. In: The United States Pharmacopeia and National Formulary USP 36–NF 31; Rockville, MD: The United States Pharmacopeial Convention Inc.; 2013: 1111-1116.

4.       Disintegration. In: The United States Pharmacopeia and National Formulary USP 36–NF 31; Rockville, MD: The United States Pharmacopeial Convention Inc.; 2013: 305-306.

5.       Donauer N, Löbenberg R. A mini review of scientific and Pharmacopeial requirements for the disintegration test. Int J Pharm. 2007; 345(1-2): 2-8.

6.       Klute AS. Disintegration testing: Strategy for quality control testing of immediate release dosage forms in exploratory development. Am Pharm Rev. 2009; 12(5): 90-93.

7.       Zuo J, Gao Y, Almukainzi M, Löbenberg R. Investigation of the disintegration behaviour of dietary supplements in different beverages. Dissolution Technologies. 2013; 20(4): 6-9.

8.       Abrahamsson B, Albery T, Eriksson A, Gustafsson I, Sjöberg M. Food effects on tablet disintegration. Eur J Pharm Sci. 2004; 22(2-3): 165-172.

9.       Radwan A, Amidon GL, Langguth P. Mechanistic investigation of food effect on disintegration and dissolution of BCS class III compound solid formulations: The importance of viscosity. BioPharm Drug Dispos. 2012; 33: 403-416.

10.     Sreelesh B, Vaze V, Rakha P, Dhingra GA, Nagpal M, Gadge MS. Study of altered disintegration rates of pain relief drugs in different beverages. J Drug Deliv Res. 2012; 1(2): 8-15.

11.     Patel P, Bagada H, Jani A. Study of Altered Disintegration Behavior of Immediate Release Pain Medication in Different Beverages. International Journal for Pharmaceutical Research Scholars. 2013; 2(4): 333-8.

12.     Choung M., Poirier B, Crosby S, Pidgeon C. A modified USP disintegration method to simulate a tablet disintegrated in the stomach when taken with cold bevrages. AAPS J. 2007; 9(S2): 1687.

13.     Chuong MC, Taglieri CA, Crosby S, Ferullo JW, Pitwei, NG. Effect of beverages on the in vitro disintegration of immediate-release pain medications. Dissolution Technologies. 2010; 17(1): 31-37.

14.     Disintegration. In: The United States Pharmacopeia and National Formulary USP 36–NF 31; Rockville, MD: The United States Pharmacopeial Convention Inc.; 2013: 305-306.

15.     Gilbert S, Anderson B, Neil R. Tablets. In: Lachman L, Lieberman HA, Kanig JL (eds.). The Theory and Practice of Industrial Pharmacy. 1991:306.

 

 

 

Received on 21.01.2017       Modified on 05.02.2017

Accepted on 22.02.2017     ©A&V Publications All right reserved