Advancing oral solid dosage forms - rising trends in pharmaceuticals and nutraceuticals
Anita Solanki, Lead – White Paper & Publications, ACG Capsules; Dr. Milind Biyani, Consultant, ACG Capsules; and Dr. Jnanadeva Bhat, Head – Formulation R&D (Pharma and Nutra), ACG Capsules discuss how innovation and new developments in solid dosage forms for pharmaceuticals and nutraceuticals are being driven by the need to differentiate a company’s products those of others in these highly competitive areas of business.
在整个年龄、医药产品been available in a variety of dosage forms. From time to time we see the introduction of innovative new dosage forms, such as oral films, needleless syringes, wearable injectors or skin implants. However, despite the wide range of dosage forms available, the demand for oral solid dosage forms remains unparalleled and dominant in both the pharmaceutical and nutraceutical sectors.Whilst the nutraceutical market almost exclusively focuses on oral administration for dietary supplements, a range of dosage forms are often utilized in the pharmaceuticals segment, including injectable, topical, rectal and pulmonary in addition to oral dosage forms.
Innovation in all these fields is fueled by the need to differentiate, and to deliver sustainable, advanced products in the crowded pharmaceutical and nutraceutical markets.
The enduring popularity of oral solid dosage forms
First, this form is well understood and accepted globally and has major advantages, including ease of consumption, handling and patient compliance. However, there are always improvements to be made in these areas, and oral solid dosage forms offer an excellent platform for creating products which further advance patient experience and compliance.
Second, the massive demand for oral solid dosages has ensured the introduction of innovative technologies and materials to suit the specific needs of emerging consumer groups, new active ingredients, and varied formulations. As a result of the huge variety of options, sizes and sophisticated manufacturing processes available for solid dosage forms, they are a well-suited and cost-effective option to develop new products, or to improve existing formulations. Additionally, there is a drive to incorporate newer therapeutic forms such as peptides and biologics into easily consumable oral forms.
Rising trends: pharmaceuticals
Patient-centric pharmaceutical drug design has become increasingly important, and it continues to be one of the most significant trends in medicine. This is, in part (particularly in the nutraceutical sector), due to the market becoming more saturated, thus resulting in a growing need to differentiate and to operate from a more consumer-focused perspective. The FDA is also encouraging patient-focused drug development which will ensure that patients’ needs and concerns are incorporated into the drug development and dosage form.
One of the primary ways manufacturers can make drugs more patient-friendly is by creating solid orals that are easier to swallow and handle. This is especially important for pediatric and geriatric populations. For these groups, formulating medicines into sprinkle capsules, mini- or micro-tablets can improve the consumer experience, as well as overall compliance. Fast-dissolving, fast-dispersing, or fast-melting formulations are also more accessible to these consumers. Other methods of providing patient-friendly dosages include segmented easy-to-score tablets, gel-forming easy-to-swallow oral films, multiple scored tablets, and solid dosage pen devices.
Concealing unpleasant tastes and odours is also critical for patient-centred care. Hard capsules can offer an advantage in cases where masking taste and odour is necessary due to their low oxygen transmission rates (OTR).
Counterfeiting continues to threaten consumer safety and brand reputations. A new way of fighting fake medicines is emerging that involves making micro tags of inert materials such as silicon dioxide, invisible printing, and DNA printing with multiple security codes printed on their surface. The size of an average micro tag is 50–110 microns, which enables them to be printed inside or outside the capsule surface without changing existing manufacturing processes. For tablets, these tags can be included in coating or printing.
Complex oral delivery for novel therapeutics
Novel forms of therapeutics are emerging, including insoluble drugs, biologics, and peptides. For the delivery of these, complex dosage forms are being created.
In 2015, it was reported that the majority of failures in new drug development were attributed to the poor water solubility of that drug. Additionally, it was estimated 90% of drugs in the discovery pipeline were poorly water-soluble.1但是，现在有一些方法可以解决此问题的解决方案。微生物化或纳米铣削可降低API颗粒的大小，以提高溶解度。另一种技术涉及在载体聚合物（例如HPMC）中产生固体分散体，该分散物通过避免产生不溶性API晶体来增加溶解度。基于脂质或聚合物的系统也用于封装不溶性药物。聚合物（PLGA）颗粒，固体脂质颗粒，脂质体和反向立方相颗粒是由于需要提高溶解度而受欢迎的技术。
There is a demand for the development of oral and nasal forms of biologics and peptides to improve patient compliance, as currently these novel therapeutics are more commonly provided as injectables. Absorption enhancers, conjugation with other entities, and gastro-retentive delivery systems are increasingly being used to achieve the oral administration of these drugs.
机器人药是一个有趣的新发展。他们利用化学信号触发一系列反应，从而导致在正确的环境中给药。2The capsule-like tablet is enteric-coated and, once swallowed, travels through the gastrointestinal tract until it reaches PH >6.5, in the small intestine. The shell dissolves at the higher PH under the generation of carbon dioxide, which inflates a balloon contained within the capsule. This reaction exposes dissolvable sucrose-based microneedles which deliver the drug by piercing the intestinal wall, thus enabling it to be rapidly absorbed.3
Combination fill capsules
Utilizing combination fill technology can be beneficial for offering fixed-dose combinations, once-daily combinations, multi-drug resistance therapies, and avoiding missing doses. Combination fill capsules can also provide a variety of release profile options. For example, Immediate release (IR) with extended release (ER) or delayed release (DR).
The following provides examples of combination fill capsule options and their benefits:
- Mini- and micro-tablets deliver greater accuracy in weight variation, offer different release profile options, and facilitate controlled absorption within the gastrointestinal tract.
Advances in manufacturing methods for this drug delivery form are already being made. Innovations to various capsule filler technologies and customized solutions retrofitted to existing machines enable manufacturers to produce these specialized products by improving the financial viability of producing these medicines.
Rising trends: nutraceuticals
传统的，动物 - 鸟类明胶胶囊越来越多地被纤维素，淀粉，角叉菜胶和帕普兰（多糖）等素食材料制成的胶囊所取代。由于选择过素食主义者或素食主义者生活方式的个人人数越来越多，这种趋势加速了。基于植物的胶囊替代品，例如HPMC（羟丙基甲基纤维素）是惰性和稳定的，并且已经开发出来满足这些客户群的需求。
As the nutraceutical sector is witnessing a significant growth globally, manufacturers need to cater to individuals with a range of dietary requirements. HPMC capsule variants provide a popular alternative for consumers, as they contain no preservatives, gelatin, wheat, gluten or animal by-products.
HPMC capsules also offer a range of other benefits. Their low inherent moisture content (3-8% w/w) makes them a superior choice over gelatin capsules for formulations where moisture significantly affects the product’s stability. For example, hygroscopic ingredients or formulations filled in gelatin capsules may absorb the moisture from the shells leading to shell brittleness. In contrast, HPMC capsules are suitable for filling hygroscopic ingredients and pose no such issues. This ensures product integrity and long-term efficacy. Carbon-critical nutraceutical extracts are largely hygroscopic in nature and can also be filled in HPMC capsules. Sensitive formulations can be encapsulated in HPMC capsules, even at lower relative humidity areas, without any challenges.
Liquid-filled hard capsules
Possibilities for liquid encapsulation include capsule-in-capsule, tablet-in-capsule and pellets-in-capsule. Each of these have their own benefits and can offer increased ingredient compatibility and delivery options. As an example, in the capsule-in-capsule form, one active ingredient is dissolved or dispersed in a solvent, while the other is encapsulated in a smaller capsule and placed into the liquid-filled capsule. This segregates the two active ingredients, therefore avoiding stability or incompatibility concerns.
1.Sandeep Kalepu and Vijaykumar Nekkanti,Acta PharmaceuticaSinica B, ‘Insoluble drug delivery strategies: review of recent advance and business prospects’, Volume 5, Issue 5, (2015), p.442-453