advanced pharmaceutical technology ocular dosage form

advanced pharmaceutical technology for ocular dosage form

1. Exploration and Analysis of Innovative Eye Dosage Forms in Pharmaceutical Technology (Group Project – Advanced Pharmaceutical-Technology 0304592 ) Prof. Adi Arida ( Spring 2024) (11th June 2024 ) Group # 3 Dalal Lababidi 1820096 Bailassan Aldijani 1910238 Maryam  Alshekhli 1910373

2. Table of content Introduction Literature review Formulation techniques . Mechanism of Action, Pharmacokinetics, pharmacodynamics and uses . Challenges and future perspectives Future Technologies in Ocular Drug Delivery Conclusion References

3. 1. Introduction The complicated architecture and protective barriers of the eye make it difficult to deliver medications to the area, which limits the efficacy of traditional ocular dosage forms. Innovative ocular drug delivery systems have been developed in response to recent advances in pharmaceutical technology. These systems aim to prolong therapeutic benefits, improve patient compliance, and boost drug bioavailability. The goal of this study is to examine these novel dosage forms, looking into their creation, modes of action, advantages, drawbacks, and possible therapeutic uses. Comprehending these sophisticated compositions is essential for enhancing ocular therapies and attending to unfulfilled medical requirements in the field of ophthalmology.

4. 2. Literature review. 1. In situ gel. One of the newest techniques for ocular medication administration is in-situ gels. Upon injection into the eye, these gels experience a sol-to-gel transition that results in enhanced bioavailability and prolonged medication release. These gels are made using temperature-sensitive, pH-sensitive, and ion-sensitive polymers, according to recent investigations. For example, formulations based on poloxamer and chitosan have demonstrated potential because of their simplicity of administration and biocompatibility. Fig1.administration of in situ gel eye drop.

5. 2. Nanoparticles . Another interesting strategy is provided by nanoparticles, which allow for regulated and targeted medication release. For ocular applications, polymeric nanoparticles, lipid-based nanoparticles, and dendrimers have all been thoroughly investigated. Both hydrophilic and hydrophobic medications can be encapsulated in these nanoparticles, which improves their stability and capacity to pass through ocular barriers. The creation of surface-modified nanoparticles to enhance cellular absorption and ocular adherence is one recent discovery.

6. Fig2. drug delivery and application

7. 3. Microneedle . One least invasive method of administering medication to the posterior portion of the eye is by the use of microneedles. By making microchannels in the tissues of the eyes, these small needles can transport drugs directly to the desired locations. Since biodegradable microneedles have reduced tissue damage and increased patient comfort, research has concentrated on using polymers like polyvinylpyrrolidone (PVP) and hyaluronic acid in their construction.

8. 3. Formulation techniques. In situ gels: Polymers used in in-situ gel compositions experience phase transitions when they are exposed to particular physiological parameters like pH, temperature, or ionic strength. Typical materials consist of : A biocompatible polymer that gels in reaction to pH variations is called chitosan. Poloxamers: Polymers that gel at body temperature due to temperature sensitivity. The procedure entails adding the medication, sterilizing the finished product, and dissolving the polymer in the proper solvent. The extended duration of contact between these gels and the ocular surface improves medication absorption.

9. 1. Nanoparticles . Several crucial phases are involved in the creation of nanoparticles for ocular medication delivery : Produced with biodegradable polymers like PLGA (poly(lactic-co-glycolic acid)), polymeric nanoparticles... Either the medicine is adsorbed on the surface or it is contained within the polymer matrix. Lipid-Based Nanoparticles: Solid lipid nanoparticles or nanostructured lipid carriers are made from a formulation of lipids such as triglycerides and phospholipids. Branched macromolecules known as dendrimers have the ability to bind medications to their surface or encapsulate them within their structure. To guarantee consistent medication distribution and particle size, the production methods include solvent evaporation, nanoprecipitation, and emulsification-solvent diffusion.

10. 2. microneedle Using micromolding techniques, biodegradable polymers such as PVP or hyaluronic acid are cast into molds to create arrays of small needles, which is how microneedles are made. Drugs are subsequently inserted into these needles using coating or encapsulating techniques. Following insertion, the microneedles dissolve or break down, allowing the medication to enter the ocular tissues directly.

11. 3. Ocular prosthesis Artificial eyes, also referred to as ocular prostheses, are used in place of a missing natural eye after enucleation or evisceration. Although these devices have historically been used for cosmetic purposes, developments in drug delivery technologies have made it possible for them to be used therapeutically as well. The main formulation methods used in the creation of drug-eluting ocular prostheses are as follows: Material Selection: Because medical-grade PMMA (polymethyl methacrylate) is stable and biocompatible, it is commonly used as the foundation material for ocular prostheses. The substance may be embedded with biocompatible polymers for drug delivery, which would allow the medications to be released gradually. Drug Incorporation: Techniques like solvent casting or dispersion can be used to include drugs into the prosthetic material. These techniques guarantee that the medication is dispersed evenly within These techniques guarantee that the medication is dispersed evenly throughout the polymer matrix. To stop post-surgical infections or inflammation, for example, antibiotics or anti-inflammatory drugs can be implanted within the prosthetic. Surface Modification: The prosthesis's surface can be altered to improve drug release characteristics. Drugs can be gradually released from a surface reservoir created by methods like plasma treatment or coated with biodegradable polymers (PLGA). Controlled Release Systems: Microfabrication techniques can be used to develop micro-reservoir systems inside the prosthesis. These drug-filled reservoirs are made to release the medication at a predetermined pace, resulting in long-lasting therapeutic effects.

12. 4. Mechanism of Action, Pharmacokinetics, pharmacodynamics and uses.

13. Solid Ocular Devices Ocular Inserts : These are devices that are placed into the conjunctival sac and loaded with medicinal medications. They are separated into three categories: soluble, insoluble, and bioerodible. While insoluble inserts disperse drugs at a controlled rate through reservoir and matrix systems and require removal, soluble and bioerodible inserts dissolve gradually while dispensing medication. This system controls drug release patterns, enhances drug activity, lengthens drug residence, and improves bioavailability. Pharmacokinetics : Drugs are released from ocular implants in a regulated manner. While insoluble inserts release pharmaceuticals at a controlled rate through reservoir and matrix systems, soluble and bioerodible inserts dissolve gradually over time. The conjunctival sac and cornea are the main routes via which drugs are absorbed, while systemic absorption is also a possibility . pharmacodynamics : Improved bioavailability and a longer-lasting therapeutic impact are the results of the drug's prolonged activity and longer residence in the eye. Optimizing therapeutic results is achieved by minimizing fluctuations in medication concentration through controlled drug release patterns.

14. Solid Ocular Devices Ocular implants: Solid apparatuses that gradually release molecules from polymeric matrix in order to administer medication. Drugs are released over months to years by biodegradable implants, which use polymers such as polycaprolactones, polyglycolic acid, polylactic acid, and polylactic-co-glycolic acid. By putting them at various eye sites, they can avoid the blood-ocular barrier and transport medications directly to the target site for a prolonged amount of time, lowering the risk of infection and the need for repeat treatments. Pharmacokinetics : Over an extended period of time, ocular implants gradually release medications from polymeric matrix, resulting in sustained drug levels in the eye. While non-biodegradable implants need to be surgically removed following therapy, biodegradable implants break down over time and gradually release medications. Localized drug absorption takes place in the eye, avoiding systemic circulation. Pharmacodynamics : Ocular implants sustain therapeutic levels for a longer period of time by directly delivering a predetermined dosage of medication to the target spot. Implants decrease systemic side effects and increase treatment efficacy by avoiding the blood-ocular barrier.

15. Solid Ocular Devices Ocular Films: By topically applying these sterile dosage forms to the eye sac, ocular bioavailability is increased and drug delivery obstacles are removed. They diminish dosage frequency, lessen systemic side effects, and increase therapeutic efficacy. A detailed grasp of the medication, drug permeability limitations, and excipients is necessary for designing effective ocular films Pharmacokinetics : Extended drug residence and intimate contact with the cornea are provided by drug-eluting contact lenses, which increase the bioavailability of the drug. Drug absorption mostly happens through the cornea, while drug release happens via diffusion from the lens material. Pharmacodynamics : Better therapeutic efficacy with less systemic absorption is a result of increased medication bioavailability. Contact lenses reduce the frequency of dosage and maximize drug delivery by preserving drug levels on the ocular surface.

16. Solid Ocular Devices Drug-Eluting Contact Lenses : Drug-Eluting Contact Lenses: These lenses enhance drug bioavailability by providing prolonged drug residence and close contact with the cornea. They reduce medication requirements, dosing frequency, and systemic absorption. Techniques like molecular imprinting and colloidal polymeric nanoparticles are employed to load pharmaceuticals into contact lenses, aiding drug delivery to the posterior chamber of the eye Pharmacokinetics : Extended drug residence and intimate contact with the cornea are provided by drug-eluting contact lenses, which increase the bioavailability of the drug. Drug absorption mostly happens through the cornea, while drug release happens via diffusion from the lens material. Pharmacodynamics : Better therapeutic efficacy with less systemic absorption is a result of increased medication bioavailability. Contact lenses reduce the frequency of dosage and maximize drug delivery by preserving drug levels on the ocular surface.

17. Microneedles Fig 3.types of microneedles

18. Microneedles Solid Coated Microneedles: Mechanism of Action: The coated drug disperses when solid coated microneedles pierce the ocular tissue. When the coating is inserted, it breaks down and leaves tiny holes in the sclera or cornea. These micropores increase the porosity of the ocular tissue, which improves medication permeability. Use : Drugs are delivered via solid coated microneedles to treat a range of ocular ailments. For instance, solid coated microneedles have demonstrated enhanced absorption of pilocarpine, a medication used to treat glaucoma. Similarly, to treat corneal neovascularization, bevacizumab, an anti-VEGF pharmaceutical, has been placed onto solid coated microneedles to deliver medication to the corneal stroma in a tailored manner.

19. Microneedles Solid Coated Microneedles: Pharmacokinetics: By forming micropores in the ocular tissue, solid coated microneedles improve drug permeability and provide better drug absorption. The qualities of the coating and the medication itself determine how quickly the drug releases and absorbs. Pharmacodynamics : Solid coated microneedles help distribute drugs to specific ocular tissues by making the cornea or sclera more porous. This can increase medication bioavailability and decrease the requirement for frequent dosage, which can result in better therapeutic outcomes.

20. Microneedles Hollow Microneedles: Mechanism of Action: The complete medication formulation is contained within hollow microneedles. Drug administration into the targeted ocular tissues is made possible by the drug's leakage from the hollow spaces in the microneedles upon puncturing the ocular tissue. Use : Different drug delivery systems, such as liposomes, nanoparticles, and nano -emulsions, have been loaded into hollow microneedles. For example, hollow microneedles have been used to efficiently inject triamcinolone acetonide into the suprachoroidal area in order to treat posterior acute uveitis.

21. Microneedles Hollow Microneedles: Pharmacokinetics: By forming micropores in the ocular tissue, solid coated microneedles improve drug permeability and provide better drug absorption. The qualities of the coating and the medication itself determine how quickly the drug releases and absorbs. Pharmacodynamics : Solid coated microneedles help distribute drugs to specific ocular tissues by making the cornea or sclera more porous. This can increase medication bioavailability and decrease the requirement for frequent dosage, which can result in better therapeutic outcomes

22. Microneedles Dissolving Polymeric Microneedles: Mechanism of Action: The drug is put into biocompatible and biodegradable polymers that make up dissolving polymeric microneedles. The loaded drug is released into the eye tissue by the dissolving microneedles when they are applied to the ocular tissue. Application : The therapeutic effect of a number of medications has been considerably enhanced by dissolving polymeric microneedles. Dissolving polymeric microneedles, for instance, were an efficient way to administer the weakly soluble antifungal drug amphotericin B, allowing for quick dissolution, superior tissue penetration, minimal toxicity, and sustained therapeutic benefit.

23. Microneedles Dissolving Polymeric Microneedles: Pharmacokinetics: Biocompatible and biodegradable polymers are used to make dissolving polymeric microneedles, which release the drug when they dissolve. The characteristics of the polymer and the medication's formulation affect how quickly the medicine releases and absorbs. Pharmacodynamics : Dissolving polymeric microneedles release the medication when applied to ocular tissue, improving drug permeability and bioavailability. When compared to traditional dosage forms, this may lead to increased therapeutic action and decreased dosing frequency.

24. Three-Dimensional (3D) Printable Systems Ocuserts and Ocular Prostheses: Mechanism of Action: Ocuserts , which are intended to modify the pharmacokinetics of medications, and ocular prosthesis are made possible by 3D printing technology. These inserts and prosthesis can offer improved tissue penetration, prolonged release, and therapeutic potential. They are customized to fit each patient. Application : For individuals with eye disorders, ocular prosthesis can restore facial symmetry. Ocuserts, which are produced using 3D printing, provide extended drug release and improved therapeutic effects by controlling the release of medications like ganciclovir -loaded glycerosomes . Pharmacokinetics : Modulated pharmacokinetics, improved tissue penetration, and sustained drug release are offered by 3D-printed ocular prosthesis and Ocuserts. The drug formulation, material characteristics, and design all affect the release rate and absorption. Pharmacodynamics : 3D-printed ocular prosthesis and Ocuserts can boost therapeutic efficacy, decrease dosage frequency, and improve patient outcomes by offering longer drug release and greater tissue penetration.

25. Three-Dimensional (3D) Printable Systems Artificial Corneas: Mechanism of Action: Materials including as gelatin, collagen, polyvinyl alcohol, and sodium alginate are used in the development of prosthetic corneal structures through the use of 3D printing technology. These materials can be used to create corneal structures that are permeable to nutrients and oxygen because they are biodegradable, translucent, and mechanically strong. Application : 3D printed artificial corneas offer a dependable and practical substitute for people with dietary restrictions or a medical history of corneal disorders. They also have the advantage of being quickly fabricated and possessing adequate mechanical strength. Pharmacokinetics : 3D printed artificial corneas are made to be nutrient and oxygen permeable, which makes it easier to administer and absorb drugs. The artificial cornea's design and material characteristics determine how quickly drugs release and absorb. Pharmacodynamics : 3D-printed artificial corneas offer improved tissue compatibility and mechanical strength, making them a dependable and practical substitute for genuine corneas that can improve therapeutic results for patients with corneal disorders.

26. Three-Dimensional (3D) Printable Systems Artificial Retinas: Mechanism of Action: Cytocompatibility and structural similarity to the native human retina are achieved through the use of 3D bioprinting technology. These artificial retinas may be employed in preclinical research for conditions such as retinitis pigmentosa and can help maintain retinal progenitor cells. Application : 3D bioprinted artificial retinas help with disease research, treatment development, and the creation of effective drug delivery systems for retinal disorders. Pharmacokinetics : By imitating the structure of the natural human retina, 3D-printed artificial retinas help preserve retinal progenitor cells and make it easier to administer medications to the retinal tissue. The artificial retina's design and material composition affect how quickly drugs release and absorb. Pharmacodynamics : 3D-printed artificial retinas can improve treatment outcomes for retinal illnesses by offering a platform for preclinical research and drug discovery. This is because they provide a framework that supports retinal progenitor cells and resembles the native retina.

27. Three-Dimensional (3D) Printable Systems Ocular patches, contact lenses, and punctal plugs: Mechanism of Action: Contact lenses, ocular patches, and punctal plugs with improved therapeutic potential, superior quality control, and customized designs are made possible by 3D printing technology. These devices are used to treat ocular surface diseases and dry eye syndrome, among other ocular problems. Application : 3D-printed contact lenses offer distinctive possibilities for medication administration with improved comfort and efficacy, while 3D-printed puncttal plugs and ocular patches allow precise and sustained drug delivery. Pharmacokinetics : 3D-printed contact lenses, ocular patches, and punctal plugs provide accurate and long-lasting drug delivery. The design, material characteristics, and drug formulation all affect the absorption and release rates. Pharmacodynamics : 3D-printed punctal plugs, ocular patches, and contact lenses can decrease dosage frequency, increase patient comfort, and improve treatment efficacy by offering individualized designs and improved quality control.

28. 5. Challenges and future perspectives Nanomicelles Core–shell nanocarriers known as nanomicelles are formed when hydrophobic groups in the core and hydrophilic groups in the outer shell of amphiphilic copolymers spontaneously combine. Three categories of particles exist, usually ranging in size from 10 to 100 nm: polymers, surfactants, and multi-ion composite nanomicelles . Moreover, hydrophobic interactions, hydrogen bonds, electrostatic interactions, etc. are the forces that produce polymer micelles. Positive micelles are usually produced when the hydrophobic moiety clusters within the core and the hydrophilic moiety is directed outward to enhance contact with water. Reverse micelles are aggregates that have the opposite configuration. Positive micelles are used to encapsulate, solubilize, and transport hydrophobic pharmaceuticals, while reverse nanocelles are used to encapsulate and transport hydrophilic drugs. since of their unique chemical composition, nanocelles are regarded as safe alternatives to ocular drug delivery since they have the ability to solubilize medications internally, reduce negative side effects, boost drug stability, and have an effect on extended release.

29. 6. Future Technologies in Ocular Drug Delivery Smart Nano -Micro Platforms Smart nano -micro platforms represent a significant advancement in ocular drug delivery systems. These platforms are engineered to alter their mechanical, thermal, or optical properties in response to specific stimuli, allowing for precise control over drug delivery. These platforms differ from conventional nanocarriers due to their ability to respond to exogenous (light, sound, magnetic fields) or endogenous (pH, reactive oxygen species, biological molecules) factors. This responsiveness enables site-specific drug delivery, bioimaging , and biomolecule detection, which can significantly enhance therapeutic outcomes. Key Applications: Site-Specific Drug Delivery : These platforms can deliver drugs directly to targeted sites within the eye, minimizing systemic exposure and side effects. Bioimaging : The ability to respond to stimuli can aid in imaging techniques for diagnosing ocular conditions. Biomolecule Detection : Smart platforms can detect specific biological molecules, aiding in the early diagnosis and monitoring of diseases.

30. Future Technologies in Ocular Drug Delivery Extracellular Vesicles ( Exosomes ) Exosomes are nano -sized vesicles produced by various cell types that contain proteins, lipids, RNAs, and DNAs. These vesicles play crucial roles in intercellular communication, influencing physiological and pathological processes. In ocular drug delivery, exosomes offer promising potential due to their ability to modulate immune responses and promote tissue regeneration. Key Applications: Immune-Mediated Eye Diseases : Exosomes can regulate inflammation in diseases such as Sjogren’s syndrome and corneal allograft rejection . Tissue Regeneration : Exosomes can stimulate the production of matrix components, aiding in the renewal of corneal tissue. Drug Delivery : Exosomes can be engineered to carry therapeutic agents, such as doxorubicin, to treat ocular conditions.

31. 7. Conclusion IDDS is a more effective treatment for chronic ocular conditions like glaucoma, uveitis, endophthalmitis , and retinal disease, offering less frequent administration, extended pharmacological impact, sustained activity, and bypassing ocular barriers. However, restrictions like intrusive administration and surgical removal of non-biodegradable IDDS affect patient compliance. Variations in disease course, therapy response, and disorders may necessitate changes in pharmaceutical release profiles. Adjustable delivery ocular implanted drug delivery systems face challenges due to size restrictions and increased therapy costs due to injection and retrieval methods. Pharmaceutical professionals face challenges in delivering drugs to the eye due to eye obstructions. Innovative approach-based drug delivery systems are crucial for treating eye diseases. Anti-VEGF intravitreal injections are groundbreaking for ocular angiogenesis, but they have serious side effects. Novel approach-based drug delivery systems may lead to better therapies and serve as research models. Innovative drug delivery techniques like liposomes, contact lenses, and nanomicelles can enhance treatment effectiveness. However, production methods and technology challenges hinder their application in clinical settings. Enhancing nanocarrier stability and safety is crucial. Future research should focus on developing non-invasive ODDS that cross ocular barriers, prolong drug release, and preserve therapeutic concentration. Optimizing nanocarrier properties is essential.

32. 8. References Gupta , H., Jain, S., Mathur , R., Mishra, P., & Mishra, A. K. (2010). Sustained ocular drug delivery from a temperature and pH triggered novel in situ gel system. Drug Delivery, 17(7), 500-507. Balasubramaniam , J., Kant, S., & Pandit , J. K. (2003). In vitro and in vivo evaluation of the Gelrite gellan gum-based ocular delivery system for indomethacin. Acta Pharmaceutica , 53(4), 251-261. Kouchak , M., Bahrami , A., & Amouheidari , M. (2016). Polymeric nanoparticles: new approaches for ocular drug delivery. Nanomedicine Journal, 3(4), 210-220. de la Fuente, M., Seijo , B., & Alonso, M. J. (2008). Novel hyaluronic acid-chitosan nanoparticles for ocular gene therapy. Investigative Ophthalmology & Visual Science, 49(5), 2016-2024. han , A., Liu, C., Chang, H., Duong, P. K., Cheung, C. M. G., Xu, C., & Chen, P. (2018). Self-implantable double-layered micro-drug-reservoirs for efficient and controlled ocular drug delivery. Nature Communications, 9(1), 4433. Wei , L., Wang, Y., Zou , Q., Tong, Z., Sun, X., & Zhao, W. (2014). Hollow microneedle-mediated intravitreal injection to the rabbit eye. Journal of Controlled Release, 175, 59-68. Rodriguez, A. E., & Lapena , M. (2018). New advances in ocular drug delivery systems. Expert Opinion on Drug Delivery, 15(6), 517-523. Mostafa , M., Al Fatease, A., Alany, R.G., and Abdelkader, H. "Recent Advances of Ocular Drug Delivery Systems: Prominence of Ocular Implants for Chronic Eye Diseases." Pharmaceutics, vol. 15, no. 6, 2023, p. 1746, https://doi.org/10.3390/pharmaceutics15061746.