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How Formulators Can Incorporate Pharmaceutical Delivery Technologies


How Formulators Can Incorporate Pharmaceutical Delivery Technologies

by Stephen Turner

For many years, formulators have employed various methods and concepts to optimize efficacy, performance and compliance when it comes to taking medications. Often, the active ingredient dictates the final formulation but when market and sales factors are added to the mix, it is up to the formulator to determine the most appropriate delivery vehicle. An appropriate, unique delivery option can differentiate a product in its market niche. If the product does not sell, regardless of the benefits, it will languish and eventually be lost. By making use of technologies familiar to the pharmaceutical industry, formulators in the nutritional industry can utilize an impressive arsenal of tools available to provide an end product that can and will flourish within the marketplace.

Of all the ways to get a compound into the body, the oral route is the most preferred and offers the highest degree of consumer compliance. Tablets, capsules, sachets, chewable wafers and powdered preparations are among the options. Tablets and capsules are the most common solid oral dose in the industry and can effectively deliver the intended dose. Ultimately, the materials physical properties, chemical properties and oral bioavailability determine whether the active ingredient is appropriate for a tablet or capsule. If the total volume required is high, beyond two grams, a sachet or bulk powder is the logical course of delivery. It would be difficult to justify a tablet or capsule formulation knowing it would require consuming a large number of pills at any given time. Large dosing volumes or multiple dosing reduces consumer compliance and limits the marketability of the end product. Nutraceuticals and natural therapies that require reasonable amounts, below 2 grams, should consider the tablet or capsule form.

Familiarity with technologies and practices that are widely accepted within the pharmaceutical industry can help formulators achieve success in the area of solid oral dosage form design with products that provide unique and improved performance over conventional preparations and differentiate themselves from the competition. There are several major classes of technologies that allow for controlled delivery. Each type has its advantages and disadvantages, depending on the design and release profile it was intended to achieve.

Drug delivery systems have evolved from candy coatings with the drug mixed into the coating to the combination of physical and internal concepts that allow for targeted and precise delivery within the human body. Whether designing for gastric bypass, site specific, bimodal, linear or specific needs for optimal absorption or reducing side effects, a formulator can achieve virtually anything by incorporating modern drug delivery technologies.

Delivery Systems

Simple matrix delivery systems incorporate hydrophilic polymers that swell in the presence of water or other inert materials such as waxes to control the release of the active components from the tablet or capsule. These technologies have been well utilized for more than 40 years in the pharmaceutical industry. Simple matrix systems revolve around the common principle of diffusion suppression. This is also their limiting factor. The active ingredients need to be materials that can diffuse out of the tablet or capsule in order to engineer a level of control that can be reproduced. The longevity of these systems in the market affords formulators a pool of previous examples from which to learn. For the nutritional industry, these types of technologies offer controlled release in a simple and cost effective manner but are limited to select compounds and often cannot provide patent protection on the raw material itself. When considering this type of technology, differentiation in the marketplace can be difficult to attain due to the capabilities of these systems and their longevity in the marketplace.

Multiparticulate delivery systems have diverse variations but can be generalized under one common principle. Multiparticulate systems are a plurality of granules or micro spheres that can be loaded into either a capsule or tablet. Each of the beads is sorted for a characteristic rate of disintegration. By combining a variety of release rates into a single unit dose, a unique product can be designed. Multiparticulate systems offer formulators many different options and release profiles to meet nearly any desired outcome. Unique and novel systems can offer patent protection to the products that incorporate these types of systems and can offer both a technological advantage as well as product differentiation. Multiparticulate systems are quite complex, adding significantly to the cost of design and manufacture. Often, a multiparticulate system may even require specialized equipment, further increasing manufacturing costs. Variations in the surface and coating thickness can also translate to incomplete release of the active ingredients--one shortcoming of this type of technology. Multiparticulate systems also have difficulties handling large active ingredient loads, which can limit the potential applications to compounds that are potent or require less than a few hundred milligrams of material in a single dose.

Even with the limitations on drug load, process variability and complexity, formulators in the nutritional industry use multiparticulate systems because they suit many types of materials. A formulator needs to closely weigh the decision factors for a product when looking at this type of technology. If the market cannot support the added costs to develop and manufacture this type of product, alternative technologies may need to be considered. Complexity and capabilities set multiparticulate delivery systems apart from other technologies; this is what also limits this technology in markets where price is an issue.

Osmotic pumps and other reservoir-style delivery systems are another type of technology that has done very well in the pharmaceutical industry. These systems offer unique characteristics and true rate-limited release for high levels of control and precision but require very specialized and expensive manufacturing processes and equipment. The elementary osmotic pump is built around a single or double-layered tablet that has an osmotic core. This specialized tablet is then coated with a semi-permeable membrane that is designed to allow water in to hydrate the tablet core, which swells and pushes its contents out through an orifice that is bored by a laser. Due to the cost and complexity of these systems, they are often not seen in markets that are sensitive to price, such as the over-the-counter (OTC) and nutritional industries. Reservoir-style delivery systems face similar limitations to the multiparticulate system. Drug load, processing variability and loss combined with complexity and cost limit this type of technology to specific compounds and markets.

An experienced formulator could physically or geometrically alter the dosage form to control delivery of its contents. Some recent examples of these physical-geometrical systems have been very impressive and can offer very unique release profiles and easy patent enforcement. The drawbacks to physical-geometrical systems are in the specialized equipment and processes it takes to manufacture the dosage forms. So far, these types of technology have not been very successful in proving robust, have fallen short on durability and may show variability within the body. Once again, complex versions of this type of technology do not lend themselves to the natural products industry due to cost and complexity. Simple physical alterations however, are seen in some product applications and can offer product differentiation for those product lines that can support the cost of this technology.

Controlled delivery mechanisms that combine the advantages of the complex and intricate delivery systems with the ease and cost of first generation technologies may have a distinct advantage. For example, Temple University developed a patented self-correcting matrix style technology. The patent has been assigned to Nutraceutix, which has a platform of patented technologies that can be applied to a variety of compounds. By incorporating principles from the first generation of technologies previously described and overcoming their disadvantages, these self-correcting systems can achieve many of the same results as the current high cost and complex systems yet do it in a simple and cost effective manner. One example under this platform is U.S. Patent No. 6,090,411, which utilizes an electrolyte within a directly compressed monolithic tablet to correct for the changes in diffusion and hydration rate and achieve linear release with very low excipient load. By utilizing this new state-of-the-art technology, a formulator can offer high-end control at costs acceptable to the industry and capture a good portion of the available market segment. Controlled delivery technologies also allow a formulator or company to protect their product in a highly volatile and price sensitive market. The technologies also enhance the science behind the product to further differentiate it from unprotected immediate release forms that incorporate a given raw material, reducing or eliminating potential market erosion.

By borrowing technology, expertise and experiences from the pharmaceutical industry, a nutritional formulator can offer unique and high-performance products for the consumer. These differentiated products will have longer life cycles in volatile markets and have higher sustainable gross margins when compared to products lacking intellectual or scientific protection.

Stephen Turner, director of product development at Nutraceutix Inc., is responsible for the companys research and development efforts, and is instrumental in the application of proprietary delivery technologies for dietary supplements, OTC and pharmaceuticals. He is an active member of AAPS as well as the Controlled Release Society.

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