IPI Autumn 2020

Packaging

Advanced Capsule Development for Today’s Needs: HPMC+ The use of compounds (of biologic or chemical origin), as therapeutics is as old as mankind. Traditionally, the administering of such therapeutic products to the body occurred through the mouth by swallowing. As early as 1500 B.C. therapeutic products were being enrobed with a gelatin film, which can be considered as the first attempt at a gelatin capsule development. Capsules Background Whilst the development of capsules has been relatively slow since then, more than 100 years ago the pre-manufactured empty two-piece capsule was introduced. These two-piece capsules consist of a body part that can be filled with the therapeutic agent or formulation, and a cap to close the open end to contain the product. The capsules were originally made of gelatin and quickly gained appraisal for medicinal products due to the ease of filling and administration. They also assist with taste masking from unpleasantly flavoured medicinal formulations. With the emergence of life sciences in the middle of the last century, our medical, pharmacological and pharmaceutical knowledge gradually increased. Since the 1960s, several new chemical entities now reach the market every year. Along with these new drugs, pharmacokinetics and drug delivery evolved as important sciences in their own rights. Gelatin capsules have served as enabling dosage forms to bring these new approaches to the market. For example, we can view these capsules as the forerunners of many of the new drug delivery technologies, like liquid and semi-solids, multiparticulates e.g. pellets and minitablets, as well as dry powder inhalation formulations. Defining the Desired Product Characteristic Besides the versatility of the two-piece capsule dosage form, gelatin provides some favourable material attributes such as: high mechanical robustness, fast aqueous dissolution, taste and order masking, bi-chromatic differentiation,

and ease of swallowing. Based on these attributes, gelatin capsules represent a type of “golden standard” for the administration of a vast variety of drug delivery technology. However, as pharmaceutical and medical science and technologies evolve, we are facing new challenges in the provision of effective drug products. These challenges span from access to medicines in developing countries, to highly sophisticated drug products for unmet medical needs. Whilst other drug delivery technologies are being developed, the capsules still play a crucial part in delivering affordable, accessible and even specialised medicines. In order to meet current and future challenges, it is essential Requirements

Scientific/ technical

Patient

Aspects

Science and technology continue, and will continue, to progress rapidly. The constant generation of new therapeutics and drug delivery technologies leads to the increasing demand for capsules with specific attributes in order to enable their development to the benefit of patients. Such specific attributes are derived from the target product profile (TPP) that includes all the important aspects that the finished

Targets IR MR/SR Enteric

Capsule attributes 2–3 min 10–15 min 30–45 min pH dependent

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Dissolution

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Head space humidity

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Stability

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Fine particle fraction DPI Hygroscopicity Moisture sensitivity Degradation Impurities Market access

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Mechanical resistance

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Handling Packaging

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Paediatric form Special populations

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Weight/age/body surface dosing

Swallowability Palatability Acceptability Dose titration

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Variable/flexible dosing

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Differentiation

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Polypharmacy Visual impairment Medication errors/safety

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Adherence

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Effectiveness Safety

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Swallowability Appearance Taste Order Halal Kosher Vegetarian Vegan

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Falsified medicine Substandard medicine

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Standard manufacturing Equipment/component availability Technology transfer

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Acceptability

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Religious/ preference

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Counterfeiting

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Commercial

we work on the development of two-piece capsules with specific characteristics and/ or functionalities, while maintaining the key features of versatility and commercial viability of the gelatin capsule.

Technology accessibility

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Low moisture Equilibrated moisture

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25°C/60RH 40°C/75RH

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Stress resistance Piercing/shearing performance (DPI)

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Head space humidity (e.g. multiparticulates) Capsule size

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Easy to open/ sprinkle (e.g. minitablets) Mono-chromatic Bi-chromatic Bi-chromatic/ imprint Fill volume (Fixed dose combination, multiple release) Easy to open/ sprinkle Surface properties Colour shade Size Shape

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Polymer Capsule composition

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Bi-chromatic/ complex printing Tagging

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Machineability Yield Global supply chain

Regulatory compliance

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Approval process Market access Commercialisation

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Overall manufacturing cost

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