DDS personalised medicines M.Pharma 1st Sem Pharmaceutics.pptx

M. Pharma 1st Sem, Drug Delivery System. Dept of Pharmaceutics.

1. PERSONALIZED MEDICINES & CUSTOMIZED DRUG DELIVERY SYSTEM PRESENTED BY: FACILITATED TO: Kushal S Tegginamani Dr. Anita Desai M Pharm I st Sem Professor Dept of Pharmaceutics Dept of Pharmaceutics HSK COP Bagalkote. HSK COP Bagalkote. 1

2. Contents: Personalized Medicines: Introduction. Definitions. Pharmacogenetics. Categories of Patients for Personalized Medicines. Customized drug delivery systems: Bioelectronics Medicines. 3D printing of pharmaceuticals. Telepharmacy. 2

3. INTRODUCTION: The last 20 years have seen the emergence of the concepts of P4 medicine, that are : participatory medicine. personalized medicine. predictive medicine. preventive medicine . T his has occurred mainly in parallel with the developments in clinical genetics, artificial intelligence, and digital technology. P4 medicine is particularly based on the now almost ubiquitous nature of digital technology, whether in terms of data collection , storage, and computing capacities , or in terms of the development and use of algorithms. Personalized Medicines: 3

4. It updates of gaining knowledge and information that is more specific, more targeted, and more adapted to the pathology of a given person, and to be able to analyze these data in an intelligible and useful form in order to be able to propose personalized treatment and care. The promise of personalized medicine is that through better understanding of pharmacogenomics and genetic profiling of patients especially involved in clinical trails gives more valuable data to support treatments of individuals to respond to medications and unlikely suffer adverse reactions. It is specified that “ personalized medicine is being advanced through data from the Human Genome Project ,” highlighting the crucial importance of genetics to this approach. 4

5. Definition: P ersonalized medicine : “ is an emerging practice of medicine that uses an individual's genetic profile to guide decisions made in regard to the prevention, diagnosis, and treatment of disease. Knowledge of a patient's genetic profile can help doctors select the proper medication or therapy and administer it using the proper dose or regimen ” . As per the US National Human Genome Research Institute. Genomics: Study of the entire set of genetic instructions found in a cell (DNA). Pharmacogenomics (PGx)- is the study of how a person’s genetic makeup affects that individual’s response to medications. In doing this, it aims to develop a strategy to optimize drug therapies. Data with respect to a patient’s genotype is used to try and maximize drug efficacy while minimizing adverse drug effects and drug-drug interactions. Pharmacogenetics (PGt)- The study or clinical testing of genetic variation that assists in individual patient’s differentiation response to drugs. Biomarker - is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, disease processes, or biological responses to a therapeutic intervention. 5

6. 1. WHAT IS PERSONALIZED MEDICINE? Personalized medicine is an evolving field in which physicians use diagnostic tests to determine which medical treatments will work best for each patient or use medical interventions to alter molecular mechanisms that impact health. By combining data from diagnostic tests with an individual’s medical history, circumstances, and values, health care providers can develop targeted prevention and treatment plans with their patients. 2. WHO DOES PERSONALIZED MEDICINE HELP? Personalized medicine can guide patients toward prevention and treatment strategies designed to ward off many diseases and conditions, including certain cancers, rare genetic diseases, and some chronic and infectious diseases. 6

7. 3. HOW DOES PERSONALIZED MEDICINE HELP PATIENTS? 7

8. Currently, most physicians use “one size fits all” approach.  8

9. Personalized medicines enables the selection of the right drug at the right dose for the right PATIENT. 9

10. Need for Personalized medicines: shift the emphasis in medicine from reaction to prevention. predict susceptibility to disease. improve disease detection. customize disease-prevention strategies. prescribe more effective drugs. avoid prescribing drugs with predictable side effects. reduce the time, cost, and failure rate of pharmaceutical clinical trials. eliminate trial-and-error inefficiencies that inflate health care costs and undermine patient care. 10

11. Pharmacogenomics: In pharmacogenomics, genomic information is used to study individual responses to drugs. When a gene variant is associated with a particular drug response in a patient, there is the potential for making clinical decisions based on genetics by adjusting the dosage or choosing a different drug. Scientists assess gene variants affecting an individual's drug response the same way they assess gene variants associated with diseases: by identifying genetic loci associated with known drug responses. When studying drug action in individuals, researchers focus on two major determinants: i)  How much of a drug is needed to reach its target in the body. ii) How well the target cells, such as heart tissue or neurons, respond to the drug. The scientific terms for these two determinants are pharmacokinetics and pharmacodynamics, and both are critical considerations in the field of pharmacogenomics. 11

12. Pharmacokinetics: Pharmacokinetics encompasses four processes: absorption, distribution, metabolism, and excretion . Absorption usually refers to how a drug enters the bloodstream after a person takes a pill.  Distribution describes where the drug travels after absorption and how much of the drug reaches the target site. Metabolism refers to how the drug gets broken down in the body . excretion describes how drugs leave the body, whether by urine, bile, or, in some cases, exhalation. Pharmacodynamics: P harmacodynamics is the molecular action of a drug on its target, whether this is a cell surface target (e.g., a receptor), an ion channel, or an intracellular target (e.g., an enzyme or regulatory protein).  12

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14. Pharmacogenetics: Pharmacogenetics blends important components of the disciplines of genetics and pharmacology, and aims to describe the influence of inheritance on variable drug response. This review provides an overview of the history and current status of pharmacogenetics. The role of genetics in variable drug response is now firmly established. To apply this information to the clinical setting, more sophisticated methods, such as a multiple candidate gene approach, or genomic approaches, are likely to be needed. The clinical vision for pharmacogenetics is that genetic information might be used to identify the drug(s) and dosages with the highest likelihood for benefit and the lowest risk for harm in an individual patient. 14

15. As outlined in this, it is recognized that differences in either PK or PD can lead to variable drug efficacy or toxicity risk. 15

16. Clinical potential of pharmacogenetics. Patients with the same empirical diagnosis (e.g. hypertension, leukemia, etc.) are typically treated in the same manner, although their responses to drug therapy will not be the same. Pharmacogenetics has the potential to provide a tool for predicting those patients who are likely to have the desired response to the drug, those who are likely to have little or no benefit and those at risk for toxicity. This would allow tailored therapy that should reduce adverse reactions to drugs and increase efficacy rates. 16

17. Abacavir (Ziagen) Nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV and AIDS first approved in 1998. Subsequent studies showed that patients who carry the HLA-B*5701 allele were at high risk for hypersensitivity to abacavir, due to this allele being strongly associated with a single-nucleotide polymorphism at the HLA-B*5701 locus. The label was changed to recommend pre-therapy screening for the HLA-B*5701 allele and the use of alternative therapy in subjects with this allele. 17

18. 2.Trastuzumab (Herceptin) Human Epidermal Growth Factor 2 (HER-2) positive tumors comprise 20-25% of all breast cancers and are associated with worse clinical outcomes. It is a humanized monoclonal antibody designed to target the HER2 receptor domain and today, HER2 testing is a routine part of clinical diagnosis for breast cancer patients. Likewise, due to specific biomarker data, trastuzumab is a foundation therapy for many patients with HER-2 positive breast cancer. 18

19. 3.BRCA1 celebrity case report. In 2013, US actress Angelina Jolie underwent preventive double mastectomy, and two years later, had her ovaries and fallopian tubes prophylactically removed as well. A test had revealed that she had inherited a 'faulty' gene, BRCA1, that strongly increased her risk of developing breast and ovarian cancer. Harmful mutations in the BRCA genes cause cancer down generations, and research has shown that a female BRCA1 carrier has a 60–90 %chance of developing breast cancer and a 40–60 % chance of ovarian cancer. Surgery – although not the only option – may significantly reduce the cancer risk such women face. 19

20. Advantages of pharmacogenomics: To predict a patient’s response to drugs To develop “customized” prescriptions To minimize or eliminate adverse events To improve efficacy and patient compliance To improve rational drug development Pharmacogenetic test need only be conducted once during the life time. To improve the accuracy of determining appropriate dosage of drugs, To screen and monitor certain diseases To develop more powerful, safer vaccines To allow improvements in drug discovery and development. 20

21. Limitations of Pharmacogenomics: Complexity of finding gene variations that affect drug response. Millions of SNPs must be identified and analysed to determine their involvement in drug response 2. Confidentiality, privacy and the use and storage of genetic information 3. Educating healthcare providers and patients Complicates the process of prescribing and dispensing drugs Physicians must execute an extra diagnostic step to determine which drug is best suited to each patient 4. Disincentives for drug companies to make multiple pharmacogenomic products Most pharmaceutical companies have been successful with their “one size fits all” approach to drug development For small market- Pharmaceutical companies hundreds of millions of dollars on pharmacogenomic based drug development. 21

22. Categories of patients for personalized medicine: Patients are mainly classified depending upon the: Genetic polymorphism. Epigenetics and other factors. Cytochrome p450 genetic. Different Families of enzyme polymorphism. 22

23. 1. Genetic Polymorphism: Genetic polymorphism is a difference in DNA sequence among individuals, groups or population. Variations in gene associated with pharmacokinetics and pharmacodynamic of drug may result in toxic, altered, or no response. These variants can be used for developing a biomarkers for diagnosis and therapeutics categorization of a particular diseases. The genome-wide association studies (GWAS) have discovered many genetics variants related to different lethal diseases. 23

24. 2. Epigenetic & other factors : Epigenetics factors such as age, sex, liver and kidney function, lifestyle previous diseases and adverse reaction are also decides therapeutic response of drug. Old age patient have high risk of adverse reaction due to the poor rate of physiology and metabolism. Gender-specific physiological difference such as a pregnancy and breastfeeding also affect the outcome of treatment by a drug. A level of different hormones between a male and female has been observed, which may cause different response to a drug in male and females. Environmental chemicals, drugs, and natural compounds can alter the efficacy of the drug by drug-drug interactions or drug-herb interactions. 24

25. 3.Cytochrome P450 genetic polymorphism: This group of enzymes as indicated earlier, responsible for metabolizing more than 30 types of enzyme. It can be determine how quickly and effectively these agents eliminated from body. The CYP450 test can be used to determine dosing and effects of specific antidepressant medications, anticoagulants such as warfarin, proton pump inhibitors and number of other agents. 25

26. 4. Different families of enzyme polymorphism: Thiopurine Methyltransferase: An enzyme called thiopurine Methyltransferase breakdowns a chemotherapy drug called thiopurine. It is used to treat leukemias and autoimmune disorders. Some people have genetic variations that prevent them from producing enzyme. As a result, thiopurine levels can build up in body, leading to severe toxicity. Therefore blood test can be used to check this variations before treatment begins. 26

27. B. UGT1A1 enzyme : This enzyme determines how the body breakdown irinotecan, a chemotherapy drug for treating colorectal cancer. In patient with deficiency of this enzyme the medication can build up to toxic levels, possibly causing suppression of the bone marrow, infection, and even death. Doctors can test for this genetic variation before treatment. Starts and then customize the dosage to prevent a toxic buildup of the drug. 27

28. C. Dihydropyramidine dehydrogenase enzyme: The medication 5 - fluorouracil along with its related compounds one of the most commonly used chemotherapy agents. Some people have a genetic variation that results in a decrease in the Dihydropyramidine dehydrogenase enzyme, which is responsible for breaking down 5-FU. As a result of this deficiency, some people may experience sever or even fatal reaction to 5-FU. 28

29. Customized drug delivery systems: Introduction: Drug delivery systems that are designed to release the drug as per the need of the individual or specific patient. Therapy with right drug at right dosing in the right patient. Ability to look at a patient on an individual basis will allow for a more accurate diagnosis and specific treatment plan. Customized medicines are prepared based on each patient's medical history, needs, genetics, health conditions and other factors. Genetic and metabolic data will allow drugs to be tailored to patients sub group. The customized drug release profiles required will necessitate the use of multiple types of technologies like extended release, sustained release and timed pulsatile release. Much of the innovation will come from developing a better understanding of the patient rather than the identification of new molecules. 29

30. Definition: A customized drug delivery system refers to a method or technology designed to deliver medication in a tailored manner based on individual patient characteristics, such as genetics, metabolism, or disease state. These systems aim to optimize therapeutic outcomes while minimizing side effects by delivering drugs at specific rates, times, or locations within the body. It is also known as smart drug delivery. 30

31. Advantages of customized drug delivery: Better matching patients to drugs instead of trial and error. Eliminate life-threating adverse reactions. Reduce cost of clinical trails by quickly identifying total failures and favorable response for particular backgrounds. Improved efficacy of drugs. Dosage can be controlled for the patients who need lower doses or with the needs of each individual patient. Any allergic creating ingredient can be skipped and a customized medicine can be produced for a particular individual. One size fits all prescription medicines cannot meet, so customized medicines are the only way to better health. 31

32. Customized drug delivery system includes: Bioelectronics Medicines. 3D printing of pharmaceuticals. Telepharmacy . 32

33. Bioelectronics Medicines: Definition: Bioelectronic medicine is devices that use electricity to regulate biological processes, treat diseases, or restore lost functionality. BEMS can interact with excitable tissue in 3 distinct manners: i. they can induce, ii. block & iii. sense electrical activity. Specifically, the peripheral nervous system will be at the center of this advance, as the function it controls in chronic disease is extensive. The vision for bioelectronic medicines is one of the nano, implantable devices that can be attached to individual peripheral nerves. Such devices will be able to decipher & modulate neural signaling patterns, achieving a therapeutic effect that is targeted at the signal function of a specific organ. 33

34. Components of Bioelectronic medicines: Electrode: Silicone based penetrating electrode, polymer based fine, time, life & cuff electrode arrays, Complementary metal oxide semiconductor. Material: Noble metal, Alloys, Platinum, Platinum- iridium, Gold, Laser patterned. Gold or Platinum iridium foil (12 micrometre), lithographically patterned gold or Platinum thin (300 nm), Films on polyamide or polyline, thermally evaporated Ultra Thin (35 nm). Polymer: Polyimide 19-22, parylene 23-25 , polydimethyl siloxane (PDMS) 26-28, liquid Crystal polymer 29-30, SU-8 photoresist 31, 32 , polyurethane 33, Sheet or film (polyimide). Light: Emitting diodes for optogenetic stimulation, receiving elements for wireless Power transfer, such as inductors, antennas and ultrasonic transducer . 34

35. Mechanism of Bioelectronic Medicine: 35

36. Eg.: For Bioelectrical medicine Bioelectronics in Blind Disease : For the treating retinal disease, bioelectronic medicine play critical role. Bioelectronic medicine it’s a device that is implanted in the retina, which is shown in Fig, It includes a retinal prosthesis for restoring vision to the blind, thereby significantly improving patient’s quality of life. This implantation treated blind disease. 36

37. Pacemakers : A pacemaker is a medical device that generates electrical impulses delivered by electrodes to contract the heart muscles and regulate the electrical conduction system of the heart. This wave has been a boon to patients by regulating their heartbeats. Initially they weren’t monitored electronically but eventually due to the development in the field of bioelectronics and biotechnology they work perfectly, have given life to thousands across the world, and make complex problems concerned with the heart simple. 37

38. Applications of Bioelectronic medicines: 38

39. 3D printing of pharmaceuticals: Definition: Medical 3D printing   is increasingly deployed in both clinical and research-based healthcare activities. It involves the creation of physical replicas of anatomical structures using 3D printing (also known as additive manufacturing) processes. 3D printing can produce printlets (3D printed tablets) that are individualized to a patient’s therapeutic requirements (e.g. dosage, drug combination and drug release profiles) and personal preferences (e.g. shape, size, texture and flavor)​.   A wide variety of medicines, ranging from rapidly dissolving or dispersible formulations, controlled release preparations, gastro-retentive tablets, suppositories, minitablets through 3D printing. 39

40. How does medical 3D printing work? To develop a patient-specific 3D print, digitization of a patient’s real anatomical structures must first take place. This method leverages 3D scanning techniques such as MRI, X-ray CT or 3D ultrasound to produce a volumetric image of the anatomy.  The images must be labelled, via a process called  segmentation , to isolate structures of interest and develop a 3D computer model. The techniques used here are highly varied depending on the scanning modality, anatomical subject, and image quality. Traditional approaches require significant time and expertise but programs with advanced segmentation capability such as Simple ware software can expedite this process. 40

41. This is how it works: 41

42. DICOM from MRI scan of a liver imported into Simpleware ScanIP 42

43. 3D Printing machines of Pharmaceutical medicines: 1. Binder jet printing: Binder jet printing: 43

44. 2. Dual extrusion 3D Printing: 44

45. 3. Fused Deposition Modelling: 45

46. Some images of 3D printed pills : 46

47. Advantages of 3D Printing: Flexible Design. Rapid Prototyping. Print on Demand. Strong and Lightweight Parts. Fast Design and Production. Minimising Waste. Cost Effective. Ease of Access. Environmentally Friendly Advanced Healthcare. 47

48. Disadvantages of 3D Printing: Limited Materials. Restricted Build Size. Post Processing. Part Structure. Reduction in Manufacturing Jobs. Design Inaccuracies. Copyright Issues . 48

49. Telepharmacy : The provision of pharmaceutical care through the use of telecommunications and information technologies to patients at a distance. Technologies included in telemedicine are videoconferencing, telephones, computers, the Internet, fax. The telephone has changed from a dial-and-talk instrument to a multimedia access tool. Medical devices are being attached to telephone lines to provide remote monitoring and therapy. 49

50. Objectives of Telepharmacy: To make high quality healthcare available to traditionally under privileged population. Save the time wasted by both the health care providers and patients in travelling. Case monitoring, home care and remote critical care. Reduce costs of medical care. Survey and track diseases. 50

51. Types Of Telepharmacy : Inpatient / Remote Order-Entry Review. Remote dispensing (retail/ outpatient/ discharge). IV admixture. Remote Counselling. 51

52. Inpatient / Remote Order-Entry Review: In the inpatient Telepharmacy, a pharmacist presents at a remote location and performs remote order-entry services for an inpatient pharmacy at a hospital. Pharmacist at remote location reviews medication orders prior to the hospital staff gives medication to the patient. Inpatient Telepharmacy is beneficial for the hospitals, clinics and health systems as it enables real-time mediation order examination and monitoring. In this inpatient Telepharmacy pharmacist can provide 24/7 service. 52

53. 2. Remote dispensing (retail/ outpatient/ discharge): It is also called as retail community Telepharmacy. It is licensed physical retailer pharmacy having certified pharmacy technician. A pharmacist advises and monitors the technician, analyzes prescription and carries out his or her responsibilities from a remote location via Videoconferencing or telecommunication. Many rural patients have difficulties in accessing pharmacy services due to geographic location. This remote dispensing Telepharmacy gives convenient accessibility to these patients. These remote dispensing provides an opportunity to healthcare organizations to start retail Telepharmacy sites in the areas where traditional pharmacy may not be possible. 53

54. 3. IV admixture : IV admixture is outlined by The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) as, “the preparation of pharmaceutical product which needs the measured addition of a drug to a 50ml or larger bag or bottle of intravenous fluid.” By implementing the telepharmacy in iv admixture cleanroom, hospital pharmacies may consume less time and can also save money. If the iv admixture is reviewed by a pharmacist remotely, they can save the time required to kit up and to get inside the cleanroom for reviewing the solution. 54

55. 4. Remote Counselling : Pharmacist furnishes counselling to the patients through secure, live and interactive video calls or via telecommunications. Remote patient counselling gives potential for discharge counselling, specialty counselling, etc. 55

56. How to start a Telepharmacy? Becoming familiar with the laws and rules. General principles & first point of contact. License Application National Council for Prescription Drug Programs (NCPDP) and Drug Enforcement Administration (DEA). Third Party Reimbursement. 2. Assess the need. 3. Develop community partners. 4. Secure a physical location. 56

57. Advantages of Telepharmacy: Access to healthcare system. Patient Satisfaction. Minimal Shortage Of Pharmacists. Effective Patient Counselling. Economic Benefits . Disa dvantages of Telepharmacy: Practical Challenges . Pharmacy Regulation Laws . Security . Plenty Of Time, Effort and Money . Inability To Use Technology . 57

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