PCC1 tAPP Questions: - Formulation of Drugs

1. Define the difference between a route - route of administration refers to of administration + a pharmaceutical how a drug is introduced into the dosage form ( 3 marks): body such as orally, topically, or intravenously - a pharmaceutical dosage form is the physical form in which a drug is produced + administered such as tablets, syrups, or creams. - While the route of administration determines how the drug enters the body - while dosage form determines the physical presentation of the drug for administration (depends on site of action + physiochemical prop of the drug) 2. A novel drug molecule has been shown in preclinical testing to have antimicrobial properties and has been implicated for the treatment of oral candidiasis. It has been found that the drug has the following properties and characteristics: Moderate aqueous solubility Stable in aqueous solution Rapid first-pass metabolism Low volume of distribution GI irritation (if swallowed) State an appropriate route of administration for this compound, explaining your answer? (2 marks) 3. 1/4 Topical administration - allow direction application to the affected skin - minimised systemic exposure + side effects - reduced volume of distribution for localised treatment - this method allows for targeted treat treatment - easy application + potential for better patient compliance Which of the following would be an appropriate liquid dosage form for this compound considering the local effect needed and the properties listed above? Provide justification for and/or against each option and make clear your chosen formulation (4 marks) 1) Oral solution 2) Oral suspension 3) Mouthwash 4) Tablet - the novel drug molecule's properties suggest a mouthwash is best for localised effect - oral solutions + suspensions may not target oral candidiasis effectively due to swallowing + systemic absorption / effect + it would encourage first pass metabolism - in contrast, a mouthwash can directly treat the affected area without swallowing, minimising side effects + maximising efficacy + avoiding GI tract - tablets are also not suitable for direct application to the affected area gives systemic effect 4. You have been working on a new compound which has the potential to alleviate (moderate to severe) chronic pain. The patient population being targeted requires long-term constant dosing and has the potential for poor patient compliance. The compound has the following properties: Log P of 5.8 Highly potent High oral bioavailability Good volume of distribution - Transdermal across the skin (made of lipid membrane) so it is lipophilic as can cross through the membrane - Transdermal patches - deliver a controlled amount of medication over an extended period of time, which can help maintain steady blood levels of the drug + reduce the need for frequent dosing Additionally, transdermal patches are convenient + easy to use, which can improve patient compliance What would be an appropriate route - If high oral bioavailability it could of administration for this compound, also be a tablet as a controlled drug explain your answer? (2 marks) as can give the patient 2 tablets a day instead of 4 times a day. 2/4 5. Does transdermal have high oral bioavailability? - transdermal delivery involves the absorption of drugs through the skin into the bloodstream, bypassing the G.I tract. - this route of administration typically results in lower bioavailability to oral administration 6. Advantages of transdermal delivery? - bypasses hepatic metabolism - offers sustained release - reduces side effects - enhances compliance - provides high local concentration These benefits make it ideal for drugs needing controlled release + systemic effects 7. Compound B is another compound of interest within your project team which has been highlighted as potentially beneficial for patients infected with the Zika virus. Compound B has the following properties and characteristics: Hydrolyses rapidly in water Log P of 1.9 Poor oral bioavailability Low first pass metabolism - Given its poor oral bioavailability, a suitable route of administration could be IV administration - IV administration (parental administration) would allow Compound B to bypass the G.I tract, ensuring rapid delivery into the bloodstream without being affected by first-pass metabolism. - IV = faster onset of action What would be an appropriate route of administration for this compound? - IV be more appropriate to ensure (2 marks) the compound reaches the systemic circulation in its active form 8. What does hydrolyses rapidly in wa- - break down quickly when in contact ter mean? with water - this indicates that the compound is not stable in water 3/4 9. Compound B is another compound of interest within your project team which has been highlighted as potentially beneficial for patients infected with the Zika virus. Compound B has the following properties and characteristics: Hydrolyses rapidly in water Log P of 1.9 Poor oral bioavailability Low first pass metabolism What would be an appropriate dosage form for this compound giving consideration of its intended use and properties? Provide detailed justification for your chosen dosage form (and why others may be inappropriate). 4/4 - A suitable dosage form could be IV solution - IV solutions allow for direct administration into the bloodstream, ensuring rapid delivery of the drug without exposure to the GI tract where hydrolysis may occur - this route bypasses first-pass metabolism, providing immediate systemic effects - other dosage forms like oral tablets/capsules may be inappropriate due to the compound's poor oral bioavailability + rapid hydrolysis in water, which could lead to reduced efficacy