12 long acting injectable implants

Question 1

Describe the challenges and considerations involved in formulating drugs for long-acting implants and the requirements for drugs being used this way.

Answer 1

Formulating drugs for long-acting implants involves addressing issues like:
* rapid degradation by enzymes,
* stability problems,
* and the need for repeated doses.
The drugs, often proteins or peptides with short half-lives, must be hydrophilic with a molecular weight over 700 Da. Additionally, knowledge of physicochemical properties of the drug, system, and pharmacokinetics is crucial.

Question 2

How can gene therapeutics be utilized in long-acting drug delivery systems?

Answer 2

Gene therapeutics, such as small interfering RNAs (siRNA), can be used for gene silencing to treat various diseases in long-acting drug delivery systems. This approach offers potential benefits in delivering gene-based treatments over extended periods.

Question 3

Define the types of drugs that can be successfully formulated into long-acting injections and implants.

Answer 3

Various drugs like analgesics, anesthetics, contraceptives, antipsychotics, and HIV medications have been successfully formulated into long-acting injections and implants. These formulations address the need for sustained release and improved patient compliance.

Question 4

What are the different types of long-acting drug delivery systems available?

Answer 4

Long-acting drug delivery systems include lipophilic solutions, aqueous suspensions, gels (such as injectable depot forming implants, PLGA systems, and self-assembly lipid formulations), and surgically implanted options like microtechnologies and non-biodegradable macro-sized implants.

Question 5

Describe the importance of understanding physicochemical properties and pharmacokinetics in designing long-acting drug delivery systems.

Answer 5

Designing long-acting drug delivery systems requires a deep understanding of the physicochemical properties of the drug and system, as well as the pharmacokinetic and pharmacodynamic properties of the drug. This knowledge helps in avoiding toxicities associated with elevated drug levels and ensuring effective delivery.

Question 6

Describe the different types of preformed implants and micro- and nano systems used in drug delivery technologies.

Answer 6

Preformed implants include drug stents and steroid implants. Micro- and nano-based systems consist of technologies like microspheres, liposomes, micro- and nanoemulsions, and nanosuspensions, each offering unique advantages in drug delivery applications.

Question 7

What are the advantages of injectable versus implantable long-acting implants in the context of ocular drug delivery?

Answer 7

Injectable implants offer advantages over surgery such as improved patient compliance, reduced need for specialized experts, lower costs for pre and post-surgery medications, and decreased risk of complications like cataract formation or retinal detachment.

Question 8

How does drug solubility in water influence the choice of formulation for long-acting HIV/AIDS suspension-based formulations?

Answer 8

The solubility of HIV drugs in water impacts formulation choice, with hydrophobic drugs often formulated as insoluble suspensions. Water-based formulations are preferred for improved biocompatibility and acceptance by regulatory bodies like the FDA, EMA, and MHRA.

Question 9

Explain the benefits of formulating HIV drugs as insoluble suspensions for long-acting drug delivery.

Answer 9

Formulating HIV drugs as insoluble suspensions allows for greater retention in the skin space, leading to slow release into the systemic circulation. This approach enables long-acting drug delivery lasting around 2-3 months, requiring proof of drug tolerability and ensuring drug potency.

Question 10

Describe the importance of drug potency and the use of drug combinations in long-acting HIV/AIDS formulations.

Answer 10

Potency is crucial in long-acting HIV drug formulations, especially for first-in-class drugs. Combinations of drugs are often necessary to enhance treatment efficacy, reduce the risk of antimicrobial resistance, and ensure sustained therapeutic benefits over extended periods.

Question 11

Describe the challenges associated with stability in suspension-based drug formulations and the impact of fluctuating temperatures on drug particle size.

Answer 11

Suspension-based drug formulations face physical stability issues, especially in settings with fluctuating temperatures. Maintaining drug particle size over shelf-life is crucial to prevent issues like blockage of syringes and lack of confidence in dose delivery.

Question 12

How do suspension-based formulations typically exhibit a burst effect in terms of drug concentrations in the systemic compartment, and what challenges does this pose for drug dosing optimization?

Answer 12

Suspension-based formulations often show high initial drug concentrations (burst effect) followed by a decline, making it challenging to optimize drug dosing and pharmacokinetics. Suboptimal dosing can lead to increased antimicrobial resistance in HIV therapies.

Question 13

Define flocculation in the context of suspension-based formulations and explain its significance in drug formulation.

Answer 13

Flocculation is the process where small particles in suspension aggregate to form larger clusters (flocs). This aggregation aids in easy separation of particles, ensuring homogeneity of drug distribution throughout the formulation.

Question 14

What are the key goals of using an injectable peptide-mimetic hydrogel for sustained drug delivery, especially in the context of eradicating HIV/AIDS by 2030?

Answer 14

The primary goal is to address patient medication adherence issues by providing a long-acting formulation for sustained drug delivery. This includes delivering multiple drugs over an extended period, aiming for a convenient and effective solution to combat HIV/AIDS.

Question 15

Describe the need for a multipurpose product that combines HIV treatment with contraceptive delivery and its significance in public health initiatives.

Answer 15

There is a demand for a product that can deliver both HIV treatment and contraception effectively. This multipurpose approach can enhance public health initiatives by addressing multiple health needs simultaneously, promoting convenience and adherence to treatment regimens.

Question 16

Explain the importance of stable formulations across various climatic zones for drugs targeting HIV/AIDS and the challenges associated with transport and storage.

Answer 16

For HIV/AIDS drugs, ensuring formulation stability across different climatic zones is crucial. Challenges include transport and storage issues, as formulations must remain stable despite varying environmental conditions to maintain drug efficacy and patient safety.

Question 17

Describe the mechanism of action of Degarelix (Firmagon®) in the treatment of advanced castration-sensitive prostate cancer.

Answer 17

Degarelix is a synthetic peptide-like molecule that suppresses testosterone production by binding to GnRH receptors in the pituitary gland. This reduces luteinising and follicle-stimulating hormone levels, controlling prostate cancer spread.

Question 18

How does Firmagon® differ from other hormone regulating treatments like goserelin (Zoladex®) and lanreotide (Somatuline®)?

Answer 18

Firmagon® does not rely on specific polymeric excipients or microsphere-type suspensions to form a depot for sustained release. It is both the active ingredient and the hydrogel forming platform, driving research in peptide self-assembly.

Question 19

Define the clinical potential of peptide self-assembly in long-acting therapies using Degarelix as an example.

Answer 19

Peptide self-assembly, as seen in Degarelix, offers sustained release without the need for polymeric excipients or microspheres. This concept drives research for long-acting therapies in hormone regulation.

Question 20

Describe the structural characteristics of Oxyntomodulin and its potential clinical applications.

Answer 20

Oxyntomodulin is a 37-amino-acid peptide hormone structurally similar to glucagon and GLP-1. It shows potential in treating diabetes and obesity as an appetite suppressant, with the ability to self-assemble into a nanofibrous gel for sustained release.

Question 21

How does Oxyntomodulin break down to enable sustained release, and what was its detectable duration in rat serum post subcutaneous administration?

Answer 21

Oxyntomodulin self-assembles into a nanofibrous gel that breaks down for sustained release. It was detectable in rat serum for up to five days after subcutaneous administration, showing promise for long-acting therapeutic applications.

Question 22

Explain the significance of Oxyntomodulin’s structural similarity to glucagon and GLP-1 in the context of its potential clinical use for diabetes and obesity.

Answer 22

Oxyntomodulin’s structural similarity to glucagon and GLP-1 hints at its potential dual action in treating diabetes and obesity. This similarity allows for leveraging existing knowledge on glucagon and GLP-1 pathways for therapeutic benefits.

Question 23

Describe potential challenges associated with developing long-acting formulations.

Answer 23

Potential challenges for long-acting formulations include creating zero-order kinetics, chemical modification of the parent drug, creating new API with specific requirements for approval, use of non-GRAS excipients, demonstrating safety for new materials, ensuring consistent quality of polymeric materials, poor drug stability, and dealing with burst effect and dose dumping.

Question 24

What are some key obstacles in the development of long-acting formulations?

Answer 24

Key obstacles in developing long-acting formulations include achieving zero-order kinetics, modifying the parent drug chemically, creating a new API with specific approval requirements, using non-GRAS excipients, proving safety for new materials, maintaining consistent quality of polymeric materials, addressing poor drug stability, and managing burst effect and dose dumping.

Question 25

Describe the advantages of using injectable implant forming drug delivery systems.

Answer 25

Injectable implant forming drug delivery systems offer advantages such as formulation in aqueous environment to avoid denaturation, non-surgical administration via injection, biodegradability for natural excretion, easy sterilization, improved bio-compatibility, and controlled sustained drug release.

Question 26

How can the rate of sustained drug release be controlled in injectable implant forming drug delivery systems?

Answer 26

The rate of sustained drug release in injectable implant forming drug delivery systems can be easily controlled by adjusting the composition of the formulation, allowing for precise modulation of drug release kinetics.

Question 27

Define the method of administration for injectable implant forming drug delivery systems and its advantage over surgical implantation.

Answer 27

The method of administration for injectable implant forming drug delivery systems is via injection, eliminating the need for surgical implantation of sustained release devices, making it less invasive and more convenient for patients.

Question 28

What is the significance of the biodegradability of injectable implant forming drug delivery systems?

Answer 28

The biodegradability of injectable implant forming drug delivery systems ensures that the system is removed from the body via natural excretion routes after fulfilling its intended purpose, reducing the risk of long-term complications or device removal procedures.