Oral drug delivery is currently the preferred method of administration, making up 50% of the market, as it is relatively inexpensive and often has higher patient compliance than other methods. However, not all drugs are ideally suited to this method of administration, as many exhibit poor solubility or poor permeability, as observed in Class II and IV, and, III and IV of the Biopharmaceutical Classification System (BCS) respectively. Drugs with poor solubility are of particular concern as they often fail to fully dissolve in the gastrointestinal fluid and thus their absorption into the systemic circulation can be intermittant and insufficient leading to a greater risk of underdosing, poor bioavailability and diminished therapeutic effect. This can result in poor patient compliance as a result of breakthrough symptoms. However, for BCS Class II drugs it has been found that increased solubility exerted by a solid state modification or formulation can often result in bioavailability similar to that of the more soluble Class I drugs. Although a number of methods to increase solubility already exist there is a need for dosage forms which reduce the damage to the drug and are more flexible to the needs of the patient. Also in terms of the work of CMAC, there is a growing need for continuous methods of dosage form manufacture to reduce costs to the pharma and increase the overall quality of the final product. As such the current study aims to find an innovative formulation method to increase the solubility of pooly soluble drugs. This may be achieved by dramatically changing the way many oral dosage forms are manufactured currently. With a view to reducing the risk of polymorphic changes and degradation, the conventional steps of granulation, drying and compression will be replaced. Dosage forms will be produced by inkjet printing using an aerosol jet printer which has never been used in the pharma field before. It is hoped this will give production a degree of precision with regards to drug distribution, and thus release and overall performance, unrivaled by conventional techniques. It is hoped this will allow the resultant dosage forms to be tailored to the needs of the patient in terms of release time and dose. Due to the reduced number of processing steps and the fact the system can be used in an entirely continuous manner it is hoped this will result in less damage to the drug and a better quality of product. Previous studies have found inkjet printing to be very effective in solibilising class II drugs so it is hoped that the current study will follow this trend.
The oral route is the preferred way of giving patients medication as it is relatively cheap and much easier for the patient to perform themselves. However not all drugs can be given in this manner very easily. Drugs which fail to dissolve properly in the gut cannot be properly absorbed into the surrounding tissues and thus cannot producetheir desired effect. This problem affects a surprising number of drugs and is on the rise. Equally so there is a growing need for medicines which can be adapted to the needs of the patient as not every patient is the same and some individuals will react differently to the same medication. As such the current project aims to generate a method for combating this problem which is capable of being tailored to the needs of the individual patient. To do this the traditional way of making tablets by compression using a tablet die will be replaced by inkjet printing as the tablet can be fully designed on the computer. Drugs and any additional tablet components can be mixed with solvents to form "inks" which can be printed in the same manner as traditional ink is applied to paper. It is hoped this will prove more flexible and less wasteful than traditional methods.
The key findings thus far of the project have been that inkjet printing allows a high degree of precision as it can be programmed using CAD software. It also allows a degree of flexibility as the dose of the resultant formulation can be altered in a number of ways in addition to altering the ink itself. These include nozzle size, speed and deposition design. The act of printing has also been found to alter the solid state of drugs and thus has the potential to increase the solubility of poorly soluble drugs in the presence of stabilising polymers.
|Short title||New Methods for the Production of Oral Dosage Forms|
|Effective start/end date||1/10/14 → 10/05/19|
- EPSRC (Engineering and Physical Sciences Research Council): £16,364.00