A new trendier display for the liquid medicines The food industry was the first to use stick-packs for condiments such as ketchup or mustard as well as some dairy products for children. Following this innovation in the food industry packaging, liquid or semi-solid forms in stick-packs are increasingly being used in the world of pharmaceuticals. In the 2000s, ten years after the food industry involvement, Gaviscon® (liquid for gastrointestinal problems) and Ketoderm® (gel for seborrheic dermatitis), were launched along with a number of other specialty products primarily in the OTC space. Is this a passing fad or are there real advantages being delivered by this innovative packaging? What is the real interest in liquid stick packs? Dose safety More than one report from health institutions identified the danger of drug misuse; particularly liquid oral medications in bottles. For some packaging, the manufacturer provides the dosing system: oral pipette, measuring spoon or small cup, but in other cases where nothing is provided, there is the question of choosing the right measuring utensil (e.g.: kitchen spoon). When the bottle is a dropper bottle, it is often difficult to count the right number of drops. Tests carried out with several operators have shown that the preparation of around fifty oral drops with a dropper bottle gives very random results. Results also showed that even if a calibrated dosing container is provided, it is sometimes difficult not to be mistaken between the different colors and shapes of pipettes, cups and spoons. The dose line is not always clearly visible thus, the dexterity and visual acuity of each individual gives fluctuating results as to the accuracy of the measurement. The stick-pack has an undeniable advantage because of its pre-dosed delivery mechanism. It just needs to be opened and the content must be poured into the mouth or cup. With this, the patient or caregiver is certain of the dose being administered. In the pharmacies of the hospitals that practice Daily Nominal Dispensing (DNJ), the stick-pack is acclaimed because it allows complete control for the dispensing of oral liquids. However, few drugs currently exist in this form and the therapeutic areas are limited to gastroenterology, the treatment of colds and more recently, the treatment of mild to moderate pain. However, certain treatments that require a very precise dosing, depending on the pathology (psychiatric pathologies with oral drops) or the patient’s weight (especially with young children) do not align with the characteristics of stick packs. Drug intake witness What could be more disturbing than to wonder if we or if the patient has taken their medication? Unlike a blister of tablets where you can control the intake with an empty cell, a bottled oral liquid is nearly impossible to know if a single dose has been administered. How can we be sure that the appropriate amounts of doses have been administered? The answer to this question is liquid stick packs. After the drug is taken, the empty packaging is proof that the dose has been administered. This proof can be of great value for an elderly person who has some memory problems or a stressed mother who does not remember the stage of her child’s treatment. Product Preservation The traditional bottle, which is opened and closed several times, allows for ambient air, inert or living particles, oxygen, and other possible degradants to be captured in the bottle which is now subject to deterioration. On the contrary, liquid stick-packs are not in contact with air until administration to the patient therefore, the medication is more stable over time and retains its organoleptic properties much better. Absence or reduction of preservatives The fact that the oral liquid will be packaged in a clean environment (not sterile) in an individual package, allows manufactures to not to use or reduce the amount of preservatives. Indeed, if the formula “self-preserves” in its closed packaging, there may be no need for preservatives at all. If this is not the case, formulators will need the help of smaller amounts which will be enough to avoid microbial growth in the stick-pack after manufacturing but will not be necessary to prevent external contamination since the dose is open extemporaneously and administered at one time. There will be no need to prevent back or prolonged contamination. Microbiological cleanliness The content of the stick-pack remains clean from a microbiological point of view until use, unlike the bottle where the cleaning of the dosing system is not always performed properly. In some cases patients drink their syrup directly at the bottle resulting in potential repeated microbial contamination. This practice is avoided with the stick-pack since the container, once opened, cannot be reused and will be discarded Preservation of the environment In a study presented at the Pharmapack packaging fair in Paris in February 2012, Marc Maury, Scientific Director at Unither, established a mass material packaging differential largely in favor of the stick-pack compared to the traditional pharmaceutical bottle. By comparing a 200 ml bottle of liquid and a box of 20 eco-designed 10 ml stick-packs, with a concentrated formula that reduces the volume from 15 ml to 10 ml per dose, we save a third of the total mass of the product (packaging, dosing system and excipients). With a more compact dose, resulting in less mass to transport, means proportionally less fuel used and less waste. No waste Unlike the bottle of oral liquids which must be consumed in the weeks following its opening or brought back to the pharmacy for the more conscientious, the unit dose of liquid, kept under the temperature conditions indicated, can be consumed until its date of expiration. A study from pharmacies has shown that a third of the liquid in a bottle is not used. A pharmaceutical form adapted to nomadic lifestyles Work, trips, travel, looking after young children at the nursery or at the nanny’s place, there are so many situations where taking your open bottle is not easy. Nothing could be simpler with the stick-pack. Take with you only the number of stick-packs required. They represent less weight than the opened bottle, and in addition, there is no risk of spilling it! The industrialist’s point of view: How to think of the change from the pharmaceutical bottle to the stick-pack form? For the industrial expert in the implementation of stick packs, the different points to be considered are: The concentration of the formula For adult formulations, the volume administered is conventionally 15 ml, i.e. the (theoretical) capacity of a tablespoon. If the product allows it, we can consider the same amount of active ingredient delivered in a smaller volume, thus reducing the amount of excipients, especially the controversial excipients (certain preservatives, solubilizers, sugar to only name a few). The choice of complex, packaging material for the stick-pack The “Form-Fill-Seal” technology, used for packaging in stick-packs, consists of shaping the stick around a hollow tube which surrounds the liquid supply nozzle, and sealing its edges at the same time the stick-pack is filling. Multilayer films suitable for this type of packaging contain aluminum which provides a barrier effect which protects the liquid drug. In an eco-design approach, care will be taken to use the thinnest possible layer of aluminum. An important element which plays a factor in the stability of the product is the internal layer in contact with the liquid. It will be necessary to select the internal layer having the best compatibility with the contents: PE (Polyethylene) or other polymers are often used. Another polymer, PET (polyethylene terephthalate) constitutes the outer layer of the system. Close collaboration with film suppliers is necessary in order to find the best film for each product, to ensure the stability of the formula while having good film sealing properties and allowing it to be opened by tearing at the level of the film, without using scissors or spilling the medication The filling process and equipment The process which consists in forming the tubes of foil which will give the stick-packs its shape, in filling and in sealing them must be extremely fast so that the three actions of forming, filling and sealing are done simultaneously. We will assure that the process does not create micro-cracks in the film which could impact the quality or efficacy of the product. To stay competitive with the bottle filling, a high-speed filling machine allows you to match the economics of the liquid in the bottle. Unither, world leader in liquid stick-packs Unither is a leading industrial company in the liquid stick-pack industry with three sites dedicated to the manufacturing of drugs and medical devices in France, the USA and Brazil. Specialist in the development or re-development of formulas and the choice of the best foil according to the specifics of the composition in active principle and in excipients, Unither remains competitive in stick pack technology with comparable prices for the bottle of equivalent capacity. Conclusion: the stick-pack and the bottle are complementary but the trend towards the safety of the use of drugs tends towards pre-dosed forms, without or with the least amount of preservatives while remaining environmentally friendly. ————————————————– ————————————— Christine Adam, pharmacist and graduate of ESCP-EAP Paris is currently working as a Business Development Manager at Unither and has held positions of Marketing manager, import / export manager of drugs for clinical trials and business developer within several CDMOs (Créapharm, IDPS, etc. ) present on the whole chain of development until the commercial manufacture of the drug. To discover the PDF version published in the first edition of the Pharmaceutical Post in January 2020 click here
