Date Published: January 22, 2019
Publisher: Springer International Publishing
Author(s): Madhur Kulkarni, Brijesh Vishwakarma, Samik Sen, Sandhya Anupuram, Abhijit A. Date.
Potassium chloride (KCl) syrup is widely used for the oral treatment of the hypokalemia. However, it is associated with unacceptable taste. In the present study, we sought to develop a palatable and easy to reconstitute KCl dry syrup as a commercially viable alternative to currently available KCl syrup. We explored the potential of Eudragit E100 as a taste-masking polymer to coat and improve the palatability of the KCl. With the help of fluid bed processor, KCl was coated with the solution containing varying amounts of Eudragit E100 (4, 6, 10 and 15%). Coating with 10% polymer solution enabled optimal fluid bed processing, higher entrapment of the KCl (81%) and better in vitro release profile in 0.1 N HCl and pH 6.8 phosphate buffer. A dry syrup formulation containing Eudragit E100 coated KCl with good physical and chemical stability in dry and reconstituted state was developed. The palatability of the optimized formulation and commercially available KCl syrup was evaluated using the Electronic Taste Sensing Machine. The developed formulation showed~ 2-fold better taste-masking compared to the commercial KCl syrup. Thus, present investigation describes the development of an effective alternative to the current KCl syrup that can offer better palatability, stability and patient compliance.
Hypokalemia is characterized by the potassium depletion from the body. Patients receiving diuretics treatment, those suffering from diabetic ketoacidosis or primary and secondary hyperaldosteronism often experience hypokalemia (Cohn et al., 2000). Potassium depletion due to these causes is usually accompanied by a concomitant loss of chloride. Potassium chloride (KCl) is an electrolyte of choice for the treatment of hypokalemia as it can replenish potassium as well as chloride ions in the patients experiencing hypokalemia (Shen, 1996; Gennari, 1998). Patients with hypokalemia typically require a dose between 40 and 100 mEq of potassium per day. The US FDA has approved a number of immediate and extended release KCl formulations which contain a relatively high amount of KCl (600–1500 mg) to meet the daily requirement (Mittapalli et al., 2017). Due to a relatively high dose of KCl, these formulations are bulky and are difficult to swallow especially for the paediatric and geriatric population.
Currently, KCl syrup is the only option available in India for paediatric and geriatric patients. The taste of this formulation is considered unacceptable clinically. While developing liquid oral formulations, taste masking of a drug is of paramount importance to enhance acceptance and compliance to the therapy by the patient (Faisal et al., 2018; Kaushik & Dureja, 2014). Depending on the extent of unacceptable taste, various approaches like addition of sweeteners, flavoring agents and viscosity builders (Thoke et al., 2012), complexation with cyclodextrins (Mahesh et al., 2010; Dinge & Nagarsenker, 2008; Prabhakaran et al., 2016), granulation (Pawar & Joshi, 2014), spray drying (Amelian et al., 2017a), ion exchange resins (Kouchak et al., 2018), hot melt extrusion (Pimparade et al., 2015) or conversion to a prodrug (Karaman, 2013) are employed for the taste-masking. Microencapsulation is one of the leading techniques for the taste-masking of a variety of drugs. Microencapsulation creates a physical barrier between the drug and the taste receptors in the form of a polymeric film thus leading to efficient taste masking. Although there are several ways to achieve microencapsulation, fluid bed processing is one of the most efficient, fast and economic techniques to achieve microcapsules with high yield, uniform coating and better entrapment efficiency leading to improved taste masking (Stange et al., 2014; Keser et al., 2018; Ghimire et al., 2018). In the present study, we sought to develop dry syrup formulation containing microencapsulated KCl which would not only mask the taste but also offer the advantages such as convenience of handling, lesser weight per container and overall better stability. We explored the potential of Eudragit E100 to coat and mask the taste of highly crystalline inorganic salts such as KCl which is hitherto not reported. We used commercially viable technique such as fluid bed coating to achieve Eudragit E100 coating. Eudragit E100 is a cationic amino alkyl methacrylate copolymer which solubilizes below pH 5.5 but remains insoluble at pH greater than 5.5. These solubility characteristics make it ideal for taste masking applications wherein the polymer would not dissolve in saliva (pH- 6.8 to 7.4) thus maintaining the physical barrier between the drug and the taste buds. Upon entering the stomach, it would dissolve in gastric fluids thus releasing the drug. It is safe for oral consumption and approved by the regulatory authorities (Rowe et al., 2009; Maniruzzaman et al., 2012). A number of reported studies have used this polymer for taste masking of various drugs by employing techniques like hot melt extrusion (Keating et al., 2017), spray-drying (Khan et al., 2007), spray congealing (Shah et al., 2008), granulation (Albertini et al., 2004), solvent evaporation (Douroumis et al., 2011) and fluid bed coating (Amelian et al., 2017b).
The dry syrup formulation developed using KCl coated with 10% Eudragit E 100 solution could effectively mask the unpleasant taste of the drug in comparison with marketed syrup formulation as confirmed by e-Tongue testing. The in vitro release of KCl could not be sustained beyond 30 min in acidic dissolution medium owing to limitations of using higher concentrations of Eudragit during fluid bed coating operation. Combination of Eudragit E 100 and a water insoluble polymer like ethyl cellulose could be tried in future to retard the drug release in gastric environment to effectively avoid gastric irritation and vomiting. The taste masked KCl particles could also find potential applications in food industry.