Renukra Mishra

Rapidly dissolving dosage forms (RDDFs) have become increasingly important because of their unique properties.

  They quickly disintegrate and dissolve, and can be administered without water, making them particularly suitable for paediatric and geriatric patients. Tablets are the most commonly used type of RDDF. Orally disintegrating drug delivery systems were originally devised by scientists at Wyeth Laboratories in the UK during the 1970s and this research lead to the patenting of Zydis formulations. These patented formulations a are freeze dried type of dosage form, which possesses better convenience for use, enhanced bioavailability, and higher stability of the dosage form. 

An ideal RDDF has the following properties: 					

 Ease of handling (i.e., no special requirements for packaging and processing). 

 Water is not required for administration. 

RDDFs can be manufactured by a variety of technologies, including direct compression, wet granulation, freeze drying, spray drying and vacuum drying. 

RDDFs are mostly available commercially in tablet form and are designed to dissolve/disintegrate in the patient's mouth within a few seconds, without the need to swallow or chew.

  On administration, the tablet disintegrates in less than 1 min to form a suspension that can be easily ingested. Some patented orally disintegrating tablets (ODTs) technologies are summarized in Table 1.  

Table 1 Patented technologies for ODTs.			

ODTs have high porosity, low density and low mechanical strength. Special packaging requirements are required for ODTs because of their high friability. This is more expensive and it is sometimes challenging to transport and store these tablets. There is also a major concern regarding the ease of swallowing and even the possibility of choking when using an ODT, which makes it difficult to administrate them to paediatric and geriatric patients. This has led the pharmaceutical industry to develop alternative dosage forms that dissolve quickly in the patient's mouth and release the ingredients without the need of water.

Rapidly dissolving films (RDFs) have recently gained popularity in the form of breath fresheners.

  These films are placed in the mouth and dissolve quickly to release the flavour. RDFs are already being used in breath-freshening products from Warner Lambert and Wrigley's in the US and Europe, and Boots in the UK, as well as in vitamin products. Zengen recently launched a chloraseptic relief strip in the US to deliver benzocaine — a local anaesthetic to treat sore throats. This delivery system is simply placed on a patient's tongue or any oral mucosal tissue. Instantly wet by saliva, the film rapidly hydrates and adheres onto the site of application. It then rapidly disintegrates and dissolves to release the medicament mucosal absorption or, with modifications, allows oral gastrointestinal absorption with a quick-dissolving aspect. The advantages of RDFs are: 					

Suitable candidates for RDFs are nicotine replacement transdermal delivery (NRTD), and anti-ulcer and antihistamine drugs. Antipsychotic and sleeping disorder drugs are also potential candidates for prescription products.  

Certain issues should be considered when developing RDFs:									

 Drug loading is a major concern for RDFs. It can be increased by increasing film thickness. However, this can change the characteristics of the RDF to a slowly disintegrating film.  

 Overcoming the unwanted taste of certain APIs can also be a challenge to the formulator. 

 Dry storage conditions are also essential to maintain stability.  

 Patients ingesting films of an API such as diphenylhydramine must be cautioned about the drowsiness effects it is likely to produce immediately because of the rapid action of these dosage forms.  

 The patient may easily carry the medication at all the times so he/she should be warned against taking the films beyond normal recommended dosage schedules.

One (or a combination) of the following processes may be used to manufacture the RDF:

The RDF is preferably formulated using the solvent-casting method, whereby the water-soluble ingredients are dissolved to form a clear viscous solution. The API and other agents are dissolved in smaller amounts of the solution, and combined with the bulk. This mixture is then added to the aqueous viscous solution. The entrapped air is removed by vacuum. The resulting solution is cast as a film and allowed to dry, which is then cut into pieces of the desired size. Water-soluble hydrocolloids used to prepare RDFs include: 								

Hot melt extrusion (HME) is commonly used to prepare granules, sustained-release tablets, transdermal and transmucosal drug delivery systems.

  Processing films by this technique, involves shaping a polymer into a film via the heating process rather than through the traditional solvent casting method. 

Advantages of hot melt extrusion for film formation include: 								

 Compressibility properties of the API may not be of importance.  

 Good dispersion mechanism for poorly soluble drugs. 

Articles

The authors consider the advantages of using rapidly dissolving films to accurately and effectively deliver pharmaceutical ingredients, with an emphasis on the importance of controlling moisture content and drug loading during formulation development.