Surge in demand for patient-centric dosage forms

From minitablets to stick-packs: BENEO’s filler-binder galenIQ™ makes it easy for manufacturers to meet a growing need for convenient paediatric and geriatric delivery formats

Different consumer groups have different requirements. The fact that we’re all unique drives innovation, particularly in the nutraceutical and pharmaceutical industries. And even though there is still a long way to go until every human condition can be addressed on an individual basis with high precision and efficiency, great advances are being made in certain fields. Tailored dosage forms are a perfect example, especially in light of the specific needs of young children and the elderly. Here, BENEO’s filler-binder galenIQ™ allows for the development of targeted solutions that meet current consumer demand.

 Hard pill to swallow

Swallowing a pill or tablet can be a real challenge, particularly for young children and older patients who may have to ingest medication on a frequent and regular basis. There has been ongoing debate about the age at which most children acquire the skills to swallow tablets and capsules safely. Early literature widely quotes six years as a general age from which these dosage forms may be considered suitable for children [1]. Although swallowing ability may be perceived to improve with age, some studies have reported swallowing difficulties in adolescence. In a general paediatric clinic in Denmark, nearly half (43%) of parents surveyed reported that their children aged twelve and younger experienced difficulties taking both liquids and tablets, primarily due to taste and swallowability; with problems in administering tablets more pronounced [2].

 In older patients, age- or disease-related swallowing difficulties can affect their ability to take solid oral medicines. In a survey involving 17 community pharmacies in England and Northern Ireland, 60% of patients aged between 60 and 89 said they had difficulty swallowing tablets and capsules [3].

 Convenient dosage forms on the rise

So it’s not surprising that alternative dosage forms that suit individual patient needs are on the rise. These range from chewable tablets, minitablets and effervescent tablets to powders, sachets and stick packs. The manufacture of these formats requires a filler-binder with specific technological properties – such as BENEO’s pharmaceutical grade of isomalt, known as galenIQ™.

 galenIQ™ is a disaccharide alcohol derived from beet sugar, which is largely why it has a taste profile that is very close to sucrose. This excipient can reduce the bitterness of active pharmaceutical ingredients (APIs) and contribute to a pleasant taste and mouthfeel in the final pharmaceutical or nutraceutical product. In addition, galenIQ™ offers excellent flowability, great compressibility and ensures content uniformity over a wide range of API concentrations. Furthermore, its oil-binding capacity makes it suitable as a carrier for liquisolid formulations.

In the spotlight: minitablets

Tablets are still the dominant oral solid dosage form for all kinds of APIs. New tablet formulations that promote improved patient compliance and convenience include orodispersible tablets (ODTs), minitablets, and orodispersible minitablets (ODMTs).

Minitablets are easy to take as they have a diameter of between 2 and 4 mm. They enable exact dosing, can be coated both accurately and conveniently, and offer a high degree of dispersion in the gastrointestinal tract, thereby reducing the risk of excessive localised drug concentration.

“Manufacturing minitablets requires a filler-binder with excellent flowability,” explains Dr Maj-Britt Cepok, Head of Business Development Pharma at BENEO. “The excipient should also enable the production of high-hardness tablets at low compression forces in order to avoid damaging the extremely sensitive multiple-tip punches used to make them. In addition, good taste and water solubility are important characteristics too, especially when it comes to ODMTs that are tailored for fast drug release. The agglomerated grade galenIQ™ 721, BENEO’s water-soluble filler-binder, fulfills all of these requirements.”

Successfully tested in the field

Recently, scientists have confirmed that the direct compression grade galenIQ™ 721 is highly suitable for developing ODMTs with a low drug load via direct compression [4]. The study evaluated its potential to produce minitablets with respect to content uniformity, disintegration time, drug release, tensile strength and stability. And, because the therapeutic need for this drug for children is well known [5], enalapril maleate served as the model API [4].

A prerequisite of the therapeutic success of low-dose dosage forms is high content uniformity and low mass variation. The content uniformity of the ODMTs was within the specification requirement. The formulation’s mass variation complied with the European Pharmacopoeia. The results show that it is possible to obtain sufficiently hard enalapril maleate ODMTs at low compression force.

The researchers also found that the disintegration times of these minitablets fulfilled both the European Pharmacopoeia (180s) and even the more stringent US FDA (30s) criteria, and the dissolution profiles demonstrated immediate release of the drug. In addition, the orodispersible quality attributes were preserved over seven months of storage under ambient conditions.

This study clearly demonstrates that low-dose enalapril maleate ODMTs can be successfully produced by direct compression using agglomerated isomalt as a filler-binder.

 Future of oral solid dosage form processing

When it comes to the production of tablets, one of the most popular trends at the moment is continuous manufacturing. As opposed to traditional batch manufacturing, continuous manufacturing is an integrated process where the input materials are continuously fed into and transformed, and the processed output materials are continuously removed from the system [6]. That is why high feeding performance and consistent flow of materials are crucial for continuous manufacturing. To make the most of this process, however, manufacturers need materials that are suitable for such production.

The agglomerated type of galenIQ™ 721 has a unique morphology – for example, a spherical shape and large, porous surface area. Together with its unique particle size distribution, the excipient is specifically designed for direct compression. Its low adhesion tendency and resistance to segregation ensure high blending homogeneity and good tabletability, offering benefits for continuous manufacturing too, where materials need to be processed over a long period of time.

Dr Maj-Britt Cepok comments: “Continuous manufacturing could become the future standard for production of oral solid dosage forms – and with good reason. It allows manufacturers to make cost savings and implement less complex production processes. Agglomerated types of BENEO’s pharmaceutical excipient galenIQ™ offer the right powder properties for excellent feeding performance.”

Multifunctional filler-binder

Since the galenIQ™ range is available in a wide array of particle size distributions, morphologies and levels of solubility, it is also suitable for wet granulation, roller compaction, other agglomeration processes and pan-coating. This makes it a highly flexible filler-binder. And because it is sweet-tasting, it is ideal for chewables, effervescents, syrups, powdered formulas such as sachets and many others.

Current trends show that consumers want to take their medicines and nutritional supplements in a way that is effective, yet also convenient,

galenIQ™ is ideal for handy sachets and stick packs that taste good and can be taken on the go with or without water.

 

Dr Maj-Britt Cepok, Head of Business Development Pharma at BENEO.

In addition, in medicated hard-boiled lozenges, galenIQ™ 900 provides low hygroscopicity, which promotes long shelf-life stability. Isomalt is known to form an amorphous glass that is extremely stable against degradation by heat, humidity or acids. Worldwide, it’s the most frequently used sugar replacer in hard candies — and galenIQ™ offers the same benefits in pharmaceutical quality. Compared with sugars and other polyalcohols, galenIQ™ ensures that the lozenge does not become sticky or difficult to handle, even under high temperature and humidity storage conditions, and therefore helps to reduce the need for costly protective packaging. At 25°C and up to 65% RH, it adsorbs virtually no additional water. This characteristic enables galenIQ™ to provide optimal protection, even for moisture sensitive APIs, which is a decisive advantage over other bulk excipients.

References

1. Committee for Medicinal Products for Human Use (CHMP). Reflection paper: formulations of choice for the paediatric population. 2006. https://www.ema.europa.eu/en/documents/scientific-guideline/reflection-paper-formulations-choice-paediatric-population_en.pdf Accessed 8 Sep 2022.
2. Steffensen GK, Pachai A, Pedersen SE. Peroral drug administration to children—are there any problems? Ugeskr Laeger. 1998;160:2249–2252. https://pubmed.ncbi.nlm.nih.gov/9599520/
3. Strachan I, Greener M. Medication-related swallowing difficulties may be more common than we realise. Pharm Pract. 2005;15:411–414.
4. Lura A, Luhn O, Suarez Gonzales J, Breitkreutz J. “New orodispersible mini-tablets for paediatric use – A comparison of isomalt with a mannitol based co-processed excipient.” International Journal of Pharmaceutics. 572 (2019), 118804. https://pubmed.ncbi.nlm.nih.gov/31678381/
5. WHO Model Lists of Essential Medicines for children, 2019.
6. FDA, Modernizing the Way Drugs Are Made: A Transition to Continuous Manufacturing

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