Review ENT Updates 2016;6(1):46–50 doi:10.2399/jmu.2016001009 Effervescent tablets: a safe and practical delivery system for drug administration Ka¤an ‹pci1, Tu¤ba Öktemer2, Leman Birdane3, Niyazi Alt›ntoprak4, Nuray Bayar Muluk5, Desiderio Passali6, Andrey Lopatin7, Luisa Bellussi6, Ranko Mladina8, Ruby Pawankar9, Cemal Cingi10 1Department of Otorhinolaryngology, Ankara Koru Hospital, Ankara, Turkey 2Department of Otorhinolaryngology, Polatl› Can Hospital, Ankara, Turkey 3Department of Otorhinolaryngology, Yunus Emre State Hospital, Eskiflehir, Turkey 4Department of Otorhinolaryngology, Tuzla State Hospital, Istanbul, Turkey 5Department of Otorhinolaryngology, Faculty of Medicine, K›r›kkale University, K›r›kkale, Turkey 6Department for Otorhinolaryngology, Head and Neck Surgery, Siena University, Siena, Italy 7ENT Department, State Policlinic No1, Business Administration of the President of Russian Federation, Moscow, Russia 8ENT Department, University Hospital Rebro-KBC Zagreb, Zagreb, Croatia 9Division of Allergy, Nippon Medical School, Tokyo, Japan 10Department of Otorhinolaryngology, Faculty of Medicine, Eskiflehir Osmangazi University, Eskiflehir, Turkey Abstract Özet: Efervesan tabletler: ‹laç kullan›m› için güvenli ve pratik bir uygulama sistemi Effervescence is defined as the evolution of gas bubbles from a liquid as a Efervesans, bir s›v› içinde oluflan kimyasal reaksiyon sonucu, çözünme result of a chemical reaction. For medicinal use, effervescent tablets have ve gaz kabarc›klar›n›n oluflmas› olarak tarif edilmektedir. T›bbi kulla- specific characteristics that allow rapid adsorption of the intended drug. n›mda efervesan tabletler, verilen ilac›n h›zl› emilimini sa¤lamaya yöne- In this manner, a medication can be absorbed easily and effectively if it lik bir özellik tafl›maktad›r. Verilen ilaç, e¤er su içinde yeterli dozda ve dissolves easily in water and is present at a sufficient dose. Common acids kolayca çözünürse daha h›zl› ve etkin flekilde emilim sa¤lanacakt›r. Kö- utilized for effervescent reactions are citric, malic, tartaric, adipic and pürme reaksiyonu için genellikle sitrik, malik, tartarik, adipik veya fu- fumaric acids. Citric acid is most commonly used for this application, marik asitler kullan›lmaktad›r. En s›k tercih edilen, ürüne hafif bir li- which also adds a citrus-like taste to the products. Tartaric, adipic and mon aromas› da veren sitrik asittir. Tartarik, adipik ve fumarik asitler, fumaric acids are usually used in small amounts, due to their low water suda çözünürlükleri daha düflük oldu¤u için daha az miktarlarda kulla- solubility. Effervescent tablets are used to simplify the handling of doses, n›l›rlar. Uygun ilaç dozu al›m›n›n sa¤lanmas›, ilaca uyumun kolaylaflt›- provide optimal compatibility, promote superior and rapid absorption, r›lmas›, h›zl› ve daha iyi emilim, hastan›n s›v› al›m›n›n art›r›lmas› ve bü- increase a patient’s liquid intake and circumvent the difficulty of swallow- yük tabletlerin yutulma zorlu¤unun ortadan kald›r›lmas› için efervesan ing large pills. This review defines effervescent tablets in terms of the tabletler kullan›lmaktad›r. Bu derlemede, teknolojik aç›dan efervesan technology and describes the advantages and disadvantages. tabletler de¤erlendirilmifl, avantaj ve dezavantajlar› tan›mlanm›flt›r. Keywords: Effervescent, tablet, advantages, disadvantages. Anahtar sözcükler: Efervesan, tablet, avantaj, dezavantaj. Medications such as pills are the forms generally used, longed. In liquid forms of the medication, the delay is avoid- whereas they have some disadvantages. Slow absorption is ed. Many drugs do not have enough stability levels in the the important disadvantage as the onset of action gets pro- suspension form. Gastric residence also affects drug delivery Correspondence: Ka¤an ‹pci, MD. Department of Otorhinolaryngology, Ankara Koru Hospital, Online available at: Ankara, Turkey. www.entupdates.org e-mail: [email protected] doi:10.2399/jmu.2016001009 QR code: Received: January 4, 2016; Accepted: March 22, 2016 ©2016 Continuous Education and Scientific Research Association (CESRA) Effervescent tablets: a safe and practical delivery system for drug administration which is predicted before. Gastro-retentive preparations are of adipic, tartaric, malic and fumaric are also used. Alkali created to manage gastric residence. Another form of the sources are Potassium carbonate and bicarbonate, and drugs is effervescent tablets.[1] Effervescent mixtures and sodium carbonate and bicarbonate. When considering low powders, and compound effervescent powders including cost, high solubility and intensity of reaction, sodium car- saline cathartics are also used.[2] bonate is preferred.[15] Excipients, water-soluble lubricants [15] In effervescent technology, gas bubbles occur from the and colors, flavorings and sweeteners are also added. liquid after chemical reaction. Alkali metal bicarbonates Polyvinylpyrrolidone (PVP) is used as binder in effer- and acids (mainly citric or tartaric) are used to make effer- vescent. Its form is as dry powder or wet forms of aqueous vescence. The reaction occurs after adding water.[3–5] The or hydroalcoholic solutions. Mannitol and PEG 6000 are main issue is acid-base reaction. The basic component is other effective binders.[15,16] When using tablet press sodium bicarbonate and acidic component is citric acid.[5] machine, relative humidity should be low (≤25%) and [5] Effervescent tablets have specific characteristics that temperature should be at room temperature (25°C). To allow rapid adsorption of the drug. The drug can be obtain excellent flowability, production is made by direct absorbed easily when it displays adequate dissolution in compression method. Size of the particles should be equal. [13,17] water and is present at a sufficient dose.[6] Potassium citrate In granules, particle size should be small. To achieve has these characteristics. In case of kidney stones contain- agglomeration of the particles, monohydrate citric acid is ing urate and calcium, Potassium citrate is used which is released in the fusion method (at 54°C). Using a nonreac- helpful to decrease the prevalence of the stones.[7] Patients tive solution, such as ethanol or isopropanol, granulation with kidney stones should take too much water to use is achieved. 0.1–0.5% water is enough for active solu- effervescent easily. Potassium citrate powders are given tion.[15] The control of effervescent tablets is performed by with packages and the dose is measured. Therefore, a conventional similar tablets. The control parameters are study has been aimed to design and formulate potassium weight, hardness, pH, solution time and friability.[8,15] citrate effervescent tablets. They decrease calcium oxalate Potassium citrate is soluble in water, but insoluble in [8] and urate stones. alcohol.[7] It is used in metabolic acidosis and replaces sodi- um bicarbonate. It can also be used in urinary tract infec- Definition of Effervescent Tablets tions as an alkalizing agent. It decreases the formation of [18–21] The chemical reaction occurs in effervescent tablets. It is kidney stone induced by calcium oxalate and urate. related to acid-base reaction. At the end, carbon dioxide is Therefore, oral supplements with potassium citrate pre- released. Tartaric, malic, fumaric, citric and adipic acids vent hyperkalaemia, because it can be absorbed from gas- [8,21] are utilized. Due to the citrus-like taste, citric acid is usu- trointestinal tract highly. ally preferred for effervescents. Malic acid is expensive, Effervescent tablet solution was compared with stan- whereas it adds smoother taste. The low water-soluble dard tablets in 242 patients. The formulations contained agents are fumaric, malic and tartaric acids. So, they can be 1000 mg acetaminophen. The patients had moderate or [9] consumed in small amounts. severe pain due to the dental surgery. Both of them were In effervescent technology, when organic acid and evaluated in terms of pain intensity and relief. They were bicarbonate get together in the water, carbon dioxide is both effective compared to placebo. Onset of analgesia released. The solving process is seen in 17–20°C water. was 20 min in effervescent tablet and 45 min in standard They may be easily carried and used. Their taste is pleas- tablet. Median pain relief time was 15 min faster in the ing. The foam of them helps to kill the local bacteria. In effervescent tablet.[22] traditional Chinese Medicine, similar techniques and Recently, effervescent antibiotics have been launched [10] materials are used to prepare similar medicine. on the market. Consumption of the drug as a half glass of After the reaction of effervescent tablets, simultaneous liquid seems easier than swallowing a large tablet. carbon dioxide is produced. Their contents are com- Particularly in patients with a sore throat or swallowing pressed mixture of acids and sodium bicarbonate.[11] They disorder, this delivery method improves the quality of life rapidly dissolve in the water. When the patients have with easier and faster uptake of the drug. Furthermore, problem with capsule or tablet swallowing, these agents effervescent tablets have storage advantages for keeping can be used easily.[12,13] These tablets are also absorbed the drug dry, stable and safe compared with syrup or sus- faster.[14] The main acid used is citric acid. The other acids pension forms. Volume 6 | Issue 1 | April 2016 47 ‹pci K et al. Effervescent Tablet Technology During production, hydroscopic materials are used to The