Patient noncompliance costs the pharmaceutical industry approximately $564 billion annually.1 Despite the fact that patients typically prefer oral administration, one of the biggest contributors to medical nonadherence is dysphagia, or the inability to swallow traditional tablets and capsules. Dysphagia significantly affects the geriatric population, for example, as much as up to 68% of nursing home residents, 7% up to 30% of elderly admitted to the hospital, 8% up to 64% of patients after stroke, and 13%–38% of elderly living independently.2 Other factors leading to poor medication adherence include bad taste and inconvenient dosing.In fact, administering oral medications to pediatric, geriatric and mentally ill patients can be challenging. With children, there is a choking concern with solid dosage forms. Liquid medications are therefore often preferred, but dosing accuracy can be a problem with these products since a calibrated cup or device is needed to ensure uniform dosing. They may also contain undesirable additives, such as preservatives and dyes, and the stability of the API can be an issue. Geriatric patients in acute care facilities who are bedridden or suffer from conditions that affect swallowing often struggle taking their oral medications. Patients who are mentally ill often use a technique called “cheeking” to avoid swallowing medication, which can significantly affect their treatment results.
“Interventions to improve medication adherence should be a top priority for the pharmaceutical industry and will prove beneficial to all stakeholders,” according to Capgemini, the international consulting firm. “Increasing adherence rates by only ten percentage points would translate into a $41 billion pharmaceutical revenue opportunity in the U.S. ($124 billion globally), accompanied by improved health outcomes and decreased healthcare spending.”3
Patients are more likely to take their medication as directed when the dosing regimen fits into their lifestyle and is convenient and discrete. Ease of administration is also important for the caregiver for pediatric, geriatric, non-ambulatory patients and the mentally ill.
Orally Disintegrating Dosage Forms (ODDs), such as tablets and mini-tablets, disintegrate rapidly on the tongue within 30 seconds without the need for chewing or use of liquids, while powder forms rapidly disperse in the oral cavity. As a result, they are advantageous for all patient groups and comprise the fastest growing segment of the drug delivery market.4 Indeed, market research studies have shown that patients prefer orally disintegrating tablets over conventional tablets and would ask their doctor for, or purchase, this type over regular tablets or liquids.5
Furthermore, dispersion in saliva in the oral cavity may result in pre-gastric adsorption for some drugs, bypassing first-pass liver metabolism and leading to a faster onset of action, which can be particularly advantageous for certain indications such as migraines. Avoiding first-pass metabolism also enables a much larger proportion of the dose to reach the desired site of action, potentially allowing for lower dose requirements and, in turn, reduced side effects.
The most promising area of development for ODDs is in Pediatrics; the European Medicines Agency’s Committee for Medicinal Products for Human Use described orally dispersible dosage forms as “having great promise for children.”6 Studies have shown that orally disintegrating mini tablets are well accepted by children as young as two years old.7
Specifically, an Orally Disintegrating Tablet (ODT) should have an in vitro disintegration time of approximately 30 seconds or less using United States Pharmacopeia disintegration test equipment. ODTs should also have a good mouthfeel without grittiness, be good tasting and appeal to the target patient group. They must be robust and not crumble when being removed from the package, and must also have sufficient physical and chemical stability for adequate shelf life without the need for overly expensive packaging.
While pediatric applications are the most promising, there are additional requirements that must be considered when formulating ODDs for this group. Size and fast disintegration are particularly important, not only to reduce choking, but also to prevent the patient from expelling the dose. Taste and texture are extremely important to ensured compliance; however, the types and quantities of sweeteners and flavors used, particularly artificial ingredients, must be carefully determined. For some excipients, there may also be established limits for use due to lack of safety data in pediatric products, or limits have been established in the Inactive Ingredient Guide. Finally, ODDs for children often require a wider range of dosage strengths, particularly at the lower end. Orally disintegrating mini-tablets have been shown to be effective in providing low-dose accuracy and the ability to accommodate a wide range of doses.
Life Cycle Management opportunities represent another key element of the appeal of patient-friendly dosage forms. Companies can use these dosage forms as a way to enter new markets, extend product lines and expand into previously unsupported patient populations, while also extending their patents and trade- marks, as well as the lives of their products. All of these activities contribute to increased revenues.
Orally disintegrating technologies can be a particularly valuable life-cycle management strategy for both branded and generic drug manufacturers. These dosage forms can help companies establish innovative leadership positions in a crowded marketplace, especially for over-the-counter products.
The success of an orally administered tablet or powder may depend on how easy and pleasant it is for patients to take. At SPI Pharma, we understand this relationship and focus on assisting our customers in developing patient-friendly dosage forms.
With core expertise in polyol chemistry, SPI has developed several Mannogem® mannitol products (spray-dried, granular and powder), for use in multiple patient- friendly oral dosage forms. Mannitol offers a pleasant, cooling effect and a smooth mouthfeel without being overly sweet (50% as sweet as sugar) in orally dispersible and orally disintegrating formulations. It also is a strong, durable binder with high compactability, low friability, minimal sensitivity to over-lubrication, a high dilution capacity and low hygroscopicity. As a result, Mannogem mannitol is suitable for use with a wide range of APIs and is used extensively in swallow, chewable, and orally dispersible applications. Its high solubility may also help to facilitate rapid dissolution and improve the solubility of poorly soluble drugs.
Effer-Soda® is, like Mannogem, part of the wide range of functional excipients that SPI offers. It is a highly stable, surface-modified sodium bicarbonate that is used in effervescent tablet and powder formulations. Effer-Soda containing products, when dropped into a glass of water, create patient-friendly dosage forms that dissolve readily, are easy to take and taste pleasant.
Demonstrating true innovation in the formulation of patient-friendly ODTs, in 2002 SPI introduced Pharmaburst®, the first coprocessed drug delivery platform for the manufacture of robust, rapidly disintegrating tablets using standard tableting equipment. Approximately 60 drug products have been commercialized worldwide to date using this technology.
Use of Pharmaburst 500 (our latest product) streamlines formulation development by reducing both time and cost. Customers only need to blend in the API, flavors, sweeteners and lubricants to meet their specific needs. SPI recommends the use of sodium stearyl fumarate as the lubricant of choice, which SPI supplies under the trade name Lubripharm®, because studies have shown that there is a measurable reduction in ejection force when compared to magnesium stearate.8
The coprocessed Pharmaburst 500 system possesses optimal compactability with rapid disintegration (<30 seconds) along with a high carrying capacity that enables the formulation of ODTs, even at higher dosage levels. It is also designed with attractive organoleptic properties. Notably, Pharmaburst is not only cost-effective, but also provides reduced time to market for product line extensions and entry into new markets and patient populations.
Pharmasperse® from SPI is designed for the formulation of patient-friendly orally disintegrating powders and can be combined with SPI’s Actimask® taste-masked acetaminophen and ibuprofen actives. Powder formulations are easily poured from sachets or pouches into the mouth where they readily disperse and can be swallowed within 15 seconds with- out the need for water. ODPs are attractive because they allow higher dosage for- mulations that cannot be achieved with ODTs’ oral administration. Pharmasperse has particular applicability in pediatric medicines and for geriatric use in sachets and stick packs, removing the need to measure out a liquid dose.
It is also worth noting that taste masking in SPI’s Actimask products is achieved using gelatin in an aqueous, solvent-free coating process. In addition to acetaminophen and ibuprofen, SPI is developing the technology for other APIs. As mentioned above, Actimask can be combined with the Pharmaburst and Pharmasperse platforms to create formulations that can offer better therapeutic efficacy and bioavailability, improved stability in certain drugs, as well as obvious improvements in patient acceptability and compliance.
To help customers achieve the most effective and optimal oral dosage form solutions, including patient-friendly formulations, SPI has introduced Pharmasolutions, a comprehensive drug development service. SPI works closely with drug manufacturers to develop drug delivery platforms and/or dosage forms on a fee- for-service basis. With Pharmasolutions, SPI is seeking to become a formulation partner to the pharmaceutical industry.
In addition to improving healthcare and serving patients, SPI sees huge potential for savings to the industry through the development of patient-friendly dosage forms. Patient-friendly dosage forms fulfill the diverse needs of today’s patients and allow formulators to be creative and develop tailored products that are highly differentiated in the marketplace.
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