August 21, 2024

Manufacturing processes for oral dissolving thin films

August 21, 2024

Manufacturing processes for oral dissolving thin films.

Making Oral Dissolving Film Strips

The use of oral dissolving film strips is growing as a viable means of administration and delivery of both active pharmaceutical ingredients (APIs) and active non-pharmaceutical ingredients (ANPIs). Oral film strips are now either available, or in development for, more prescription drugs than ever before, as well as for over-the-counter medications and non-pharma supplements, such as nutraceuticals. Consumer acceptance and preference for better formulations of the substances being administered, and advancements in manufacturing technology are all part of the support behind this growth.

With the growth has also come a plethora of names by which the strips are referred to. For example, depending on the source, they are called: orally disintegrating films (ODF), orally disintegrating strips (ODS), orally dissolving strips (also ODS), oral dispersible thin films (ODTF), oral thin films ((OTF), oral fast dissolving films (OFDF), fast dissolving films (FDF), oral fast dissolving strips (OFDS), dissolving oral film strips (DOFS), dissolving oral thin films (DOTF)… Did we miss anything? You can get the picture – all the names refer to a product that accomplishes the same thing: The film strips are an ideal intraoral, fast-dissolving delivery system for both APIs and ANPIs. The names are interchangeable in that sense.

Riize Health has been a leader in the use of highly effective oral film strips for the treatment of erectile dysfunction (ED) and overall sexual health and wellness. Some sources have made mention of research and development being done for an oral film strip to treat ED. In fact, Riize has had such a product on the market for some time.

How did oral film strips get started?

The evolution of oral drug delivery began with pills – tablet and capsules. These transitioned to modified time-release tablets and capsules, to oral disintegrating tablets, to wafers and finally, to oral dissolving film strips.

The format of the film strip as a substance delivery device was introduced to the consumer market in the 1970s for personal care (breath) and over-the-counter (sore throat, nicotine) products, some of which were used orally and some topically (patches). These forms of the film strip advanced to the oral dissolving film strips being referenced here.

Among the avenues still being explored for rapid drug release products, oral film strip technology is at the forefront of continuing research and development. With the growth and increasing demand for oral film delivery, manufacturing technology for the drug and film strip products has advanced to meet that demand.

What are oral film strips made of?

Despite their obvious benefits, earlier generations of oral film strips were limited in their stability and the dosage amounts they could reliably deliver. However, innovations in drug formulas and manufacturing technology changed that, driven by the need and demand for more effective and convenient drugs and drug delivery methods. Oral film strips are easy to handle and administer, and are straightforward and cost-effective to manufacture and package. Their ease-of-use also increases patient compliance.
Oral dissolving films are composed of single or multiple polymer-based layers. The dose of the API (or NAPI) is controlled by the size and thickness of the film. The API is either dissolved or held in suspension in the polymer material in the manufacturing process. Recently, new techniques have been developed to deal with solubility differences in the APIs being used, including nanoparticle technology to reduce particle size.

The general composition of oral dissolving film strips is as follows:
– The substance being administered, be it an API (drug) or NAPI (non-pharmaceutical), typically makes up between 1% and 30% of the composition.
– Water-soluble polymers, used as film formers, can make up to 50% of the composition of the film. They are what give the film a good mouth feel and allow for rapid disintegration.
– Plasticizers (such as sorbitol or castor oil) can make up between 0% and 20% of the film, depending on the mechanical needs of the particular formula. They allow for elongation and increased tensile strength in the film.
– Saliva stimulating agents increase the rate of saliva production to aid in faster disintegration and generally are 2% to 6% of the film weight.
– Sweetening and flavoring agents can be between 6% and 10% (respectively) of the film composition.
– Surfactants, when needed, are used as dispersing agents and are a negligible amount of the composition.

Multiple active pharmaceutical ingredients (APIs) can now be layered in one strip, in high concentrations, with a minimal amount of excipient ingredients added. Both water-soluble and insoluble APIs can be integrated in the same film, some with different absorption profiles. There have also been advancements in extended-release formulations, as well as enhancements for taste. Continuing advancements in oral dissolving film strips are in response to a rapidly growing market, which has increased by approximately 80% in the last ten years.

How oral film strips are made

There are four main ways in which oral dissolving film strips are manufactured. By far the most common (over 90%) is solvent casting.

Solvent casting. In this process, the water-soluble ingredients are dissolved into one clear solution with high viscosity. The drug ingredient, along with other excipients are dissolved into a solvent. Both solutions are then mixed and dried onto a petri surface, from which they are removed and cut to size. Solvent casting is an easy preparation process with low processing costs, and produces maximum uniformity in film thickness.

Lesser-known and used manufacturing methods include:

Hotmelt extrusion. The process is similar to those used in the plastics manufacturing sector, relying on heat and lack of solvents to create molten materials which are then forced through an orifice and allowed to cool. It has been used mostly for transdermal products as well as sustained release tablets and granules.

Solid dispersion. The drug is dissolved in an appropriate liquid solvent, then mixed into a polyol melt, such as polyethylene glycol, without eliminating the liquid solvent. As it cools, the components are forced through dies to create the structure of the film. A common disadvantage is that the drug solvent won’t mix well with the melted polyethylene glycol.

Rolling method. In this process, a pre-mix is first prepared, then the active ingredient is added. It has to go through a series of steps to mix and form the film from a homogenized matrix of all the substances.

Regardless of the manufacturing process used, film strips are routinely tested for thickness (uniformity within tolerances), folding endurance, drug content uniformity, swelling (in reaction to saliva) and disintegration or dissolution (time).

Riize oral dissolving film strips are manufactured with the latest in thin-film technology to ensure that is meets or exceeds all these standards, as well as providing the maximum effectiveness of the compound drug being administered. In the case of Riize strips for ED, this compound is a proprietary combination of sildenafil (Viagara®), tadalafil (Cialis®) and oxytocin.

The effectiveness of oral film strips

Oral film strips can be used buccally (between the cheek and gum), sublingually (under the tongue) or on top of the tongue. The material used to make the film is designed to dissolve when it comes in contact with the wet saliva surface in the mouth (be it the cheek or tongue). As that occurs, the active ingredients are rapidly released and absorbed directly into the systemic circulation.

The most significant advantage of oral film drug delivery is in their bioavailability. Being absorbed directly in the mouth limits exposure to the gastrointestinal tract and the effects of what’s known as first-pass metabolism. This is when the drug is first metabolized through the digestive tract, which degrades it and results in a reduced concentration of the active ingredients being delivered. The first-pass effect is often associated with the drug being metabolized in the liver, but it can also happen in other body tissues, such as in the lungs and vascular system.

Studies of some drugs have shown that only about 4% of the API was reaching the system after going through first-pass metabolism.

The tissue inside the mouth and on the tongue has a thin, highly permeable membrane structure, over a very dense presence of capillaries. The buccal mucosa is thought to have a 4-4000 times greater permeability than the skin. The thin walls of the capillaries diffuse blood directly to veins and arteries. With rapidly dissolving film strips, like Riize Strips for ED, the process of the film dissolving, and absorption of the ingredients is typically under 30 seconds, resulting in quick bioavailability.

The fast onset of the drug effect along with overall increased bioavailability is making dissolving oral film strips a growing, preferred choice for the administration of traditional drugs, biologics, supplements and possibly even vaccines.