Personalized medicines

SR/CR formulations

1. Personalized Medicines Presented By : Facilitated To : Sachin.J.Gaddimath Dr. Anita Desai M.Pharm 1 st year HOD and Professor Dept. of Pharmaceutics Dept. of Pharmaceutics HSKCOP, BAGALKOT. HSKCOP, BAGALKOT 1

2. CONTENTS Personalized medicine. 1) Dosage forms for personalized medicine. 2) Categories of patients for personalized medicine. Customized drug delivery systems. 3D printing of pharmaceuticals. Telepharmacy. Bioelectric Medicines 2

3. DOSAGE FORMS FOR PERSONALIZED MEDICINE: INTRODUCTION: Personalized medicine also referred as precision medicine holds great promise to improve health care. According to the “National Cancer Institute” personalized medicine integrates information about person’s genes, proteins, diagnosis and treat disease. It is the form of medicine that uses information from patient‘s genotype to; Initiate a preventative measure against the development of disease or condition. Select the most appropriate therapy for a disease or condition that is suited to that patient. 3

4. Definition : Personalized medicine is defined as of medical treatment to the individual characteristics of each patient that not only improves our ability to diagnose and treat disease, but offers the potential to detect disease at an earlier stage and to treat it effectively. Understanding human genome Simpler methods identify genetic information Genetic information specific to individual Preselect effective drug No toxicity L ess trial & error 4

5. Associated Definitions: 1. Genomics- Study of the entire set of genetic instructions found in a cell (DNA) 2. Pharmacogenomics (PGx) – It is a branch of pharmacology concerned with using DNA and amino acid and sequence data to inform drug development and testing. Application of genomics to study human variability in drug response. 3. Pharmacogenetics (PGt) – The study or clinical testing of genetic variation that assists in individual patient’s differentiation response to drugs. Effect of genetic variation on drug response. PGx and PGt are expected to play important role in development of better medicines with improved benefits/risk ratio for individuals. 5

6. Pharmacogenomics: The study of how genes affect a person’s response to drugs. PHARMACOLOGY (Science of Drugs) GENOMICS (Study of genes and their functions) PHARMACOGENOMICS 6

7. Pharmacogenomics: Pharmacogenomics can play an important role in identifying responders and non-responders to medications, avoiding adverse events, and optimizing drug dose. Pharmacogenomics is the field of study & examines impact of genetic variation & drug responses via biomarkers. Personalized Medicine utilizes the biomarkers , which are simply genes and proteins that can be measured to diagnose diseases. Pharmacogenomics shows how genes determine individual variability to drug response. Pharmacists would easily predict how a patient may respond to drug, with the help of a genetic test before prescribing a drug. 7

8. Pharmacogenomics Goals are: 1. Optimizing proper drug therapy, dosage for patients – increasing efficacy & safety. 2. Other benefits are by monitoring biomarkers - reduces time, cost & failure rates in clinical trials in developing new medications and increases opportunities to develop novel therapeutics. Example : Genotyping variants of Cytochrome P450 involved in metabolism of warfarin. 8

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10. Drug Response: Environmental factors and genetic factors. • Pharmacogenetic disorders (ex: plasma cholinesterase deficiency, drug acetylation deficiency) • Pharmacogenomic tests: ex: (Tests for variations in (HLA) genes) • Genes influencing drug metabolism. • Drug targets such as the epidermal growth factor receptor HER2, tyrosine kinase inhibitors and the main target for warfarin is vitamin K epoxide reductase (VKOR).   10

11. Pharmacogenetics: 11

12. 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. 12

13. PHARMACOGENETICS IN CLINICAL PRACTICE: • The development has been slowed by various scientific, commercial, political and educational barriers. 3 major types of evidence that should accumulate in order to implicate a polymorphism in clinical care. 1) Screens of tissues from multiple humans linking the polymorphism to a trait; 2) Complementary preclinical functional studies indicating that the polymorphism is linked with the phenotype; 3) Multiple supportive clinical phenotype/genotype studies 13

14. CATEGORIES OF PATIENTS FOR PERSONALISED MEDICINE: Patients are mainly classified depending upon the genetic polymorphism: Cytochrome p450 genetic polymorphism. Different families of enzymes polymorphism. 14

15. Focusing on genomics, we have identified three categories: 1) Optimizing drug response: gene-drug interactions: A person's genetic constitution can be determined in order to address gene-drug interactions. The aim is to optimize drug efficacy and to minimize adverse events from drug treatment. Applications include genetics-based and genomics-based tests that commonly target medicines that are administered to populations with a specific gene variant. In gene-drug interactions, the focus is directed to either metabolism genes or genes related to the immune system. 15

16. 2) Gene-based drug targeting: Another area of individualization is the development of molecular mechanism specific treatment, also called gene-based drug targeting. Most research efforts are seen in the field of oncology (somatic variations) and increasing attention is being paid to genetically based diseases, such as Cystic Fibrosis. Apart from this, many research efforts are undertaken in disease areas in which there is a significant genetic association with the disease, as in the case with the VKORC1 gene in thrombosis patients. 16

17. 3) Prediction and diagnosis: Lastly, individualization efforts are undertaken to 1. Diagnose more accurately (detailed disease characterization or diagnosis of hereditary diseases that are not well-understood yet) 2. Predict risk of disease 3. These efforts provide greater insight into a patient’s constitution, contributing to a better diagnosis. 17

18. Asthma: Inhaled β2- adrenergic (e.g.Salbutamol) and corticosteroids (e.g., Beclomethasone) is the cornerstone of asthma treatment. One of the characteristics of asthma is resistance or reduced responsiveness to treatment. Until now, pharmacogenetic studies have mainly concerned the β2-adrenegic receptor gene. Additional research is needed in order to evaluate the clinical utility of genomic testing. 18

19. Diabetes: Diabetes also concerns a large patient group. While diabetes is divided into two clinical categories (type I and type II), there are at least 27 single gene mutation subtypes of diabetes that have been identified. The genetic make-up determines the clinical categorization which has been shown for several genes that cause of the syndrome designated as maturity-onset diabetes of the young (MODY). MODY patients with specific mutations often have high sensitivity to sulfonylurea’s (e.g. Glipizide). Treatment of these patients could be improved by changing the insulin regimen into a sulfonylurea’s therapy. 19

20. CUSTOMIZED DRUG DELIVERY SYSTEMS: INTRODUCTION Customized drug delivery, also termed personalized medicine, is a medical procedure that separates patients into different groups—with medical decisions, practices, interventions and/or products to the individual patient based on their predicted response or risk of disease. The terms personalized medicine contains P4 medicines. The Person: Their DNA Exposure to environmental factors Types and amount of stress they experiences What they eat 20

21. BENEFITS: Better matching patients to drugs instead of “trial and error”. Customized pharmaceuticals may eliminate life- threatening adverse reactions. Reduce costs of clinical trials by Quickly identifying total failures. Favorable responses for particular backgrounds. Improved efficacy of drugs. 21

22. DNA POLYMORPHISMS: It is the natural variations in our genes that plays a role in risk of getting or not getting certain diseases. The combination of these variations across several genes affects each individual’s risk. SNPs – a major source of variation Single Nucleotide Polymorphisms (SNPs) Single base change in DNA AAGC C TA AAGC T TA SNPs arise as a consequence of mistakes during normal DNA replication Average frequency 1/1000bp Other sources of variation are Insertions, deletions, translocation, duplications 22

23. Most common SNP Deletion Insertion Translocation 23

24. 3D printing in pharmaceuticals Introduction: 3D printing is layer by layer production of 3D objects from digital design. It include wide variety of manufacturing technologies which are all based on digitally controlled depositing of materials to create free-form geometries. this methods extensively used in field of biomanufacturing (specially for bone and tissue engineering ). It became a standard tool in automotive, aerospace and consumer goods industries. More recently 3D printing has gained traction in pharmaceutical manufacturing illustrated by FDA approval of 3D printed drug product in August 2015. It can be used for customized drug delivery system 24

25. Advantages and Applications of 3DP in Pharmaceutical Drug Delivery: (a) High production rates due to its fast operating systems. (b) Ability to achieve high drug-loading with much desired precision & accuracy especially for potent drugs that are applied in small doses. (c) Reduction of material wastage which can save the cost of production. (d)An ability to broad types of pharmaceutical active ingredients including poorly water-soluble, peptides and proteins, as well as drug with narrow therapeutic windows. 25

26. Current 3D printing technologies in pharmaceutical drug delivery: 1. Inkjet printing 2. Zip dose 3. Thermal inkjet printing 4. Fused deposition modeling 26

27. 1) Inkjet printing: Powder is used as substrate for spreading ink which solidifies into solid dosage form. 27

28. 2) Zip dose: Provide a personalized dose in addition to delivery of high drug loaded with high disintegration and dissolution levels by manufacturing highly porous material. 28

29. 3) Thermal inkjet printing: 29

30. 4) Fused depositing modeling: 30

31. Examples of pharmaceutical formulation that were developed using 3D technology: 3Dprinting Technology Dosage form Active pharmaceutical ingredients Inkjet 3DP Nanosuspension Folic acid Inkjet 3DP Implant Levofloxacin Thermal injecting printer Solution Salbutamol sulphate 3DP extrusion based printing Encapsulated within polymer (PLGA) (PVA) Dexamethasone -21-phosphate disodium salt Fused depositing model Tablet 5-aminosalysilic acid (5-ASA mesalazine) and 4-amionosalysilic acid Desktop 3D printer Tablet Guaifenesin Laboratory scale 3D printing machine Capsule Pseudoephedrine hydrochloride 31

32. TELEPHARMACY & BIOELECTRIC MEDICINES 32

33. Telepharmacy: Audio and video Still image capture Store and forward PURPOSE AND SCOPE In order to maintain or make pharmacy services available in areas that have lost their pharmacy or are in failure of losing their pharmacy, rules are necessary to permit telepharmacies. 33

34. OPERATIONS -The remote site is considered to be under the personal charge of the pharmacist at the central pharmacy. -A remote site shall be connected to its central pharmacy via computer link, video link & audio link. -A remote site should use its central pharmacy’s processing unit. -A pharmacist at the central pharmacy must approve each prescription before it leaves the remote site. 34

35. Counseling must be done by a pharmacist via video and audio link. The pharmacist must counsel the patient or the patient’s agent on all new prescriptions and refills. A pharmacist must complete monthly inspections of the remote site. Inspection reports must be included in the policies and procedures for the site. The inspection reports must be maintained until the next Board of Pharmacy Inspection. 35

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37. There are 4 types of telepharmacies: 1. Inpatient (remote order-entry review) 2. Remote dispensing (retail/outpatient/discharge) 3.IV admixtures 4.Remote counseling 37

38. 1) Inpatient (remote order-entry review) Definition Inpatient Telepharmacy refers to a pharmacist at a remote location performing remote order-entry services for an inpatient pharmacy at a hospital. The remote pharmacist reviews medication orders before the hospital staff administers the drugs to the patient. Uses Hospitals and health systems benefit from inpatient Telepharmacy as it allows for real-time medication order review and verification. With inpatient Telepharmacy, remote pharmacists are able to provide 24/7 coverage hours to help supplement and strengthen the inpatient pharmacy. 38

39. 2) Remote dispensing (retail/outpatient/discharge) Definition A remote-dispensing site, or retail community Telepharmacy, is a licensed brick-and-mortar pharmacy staffed by a certified pharmacy technician. A pharmacist supervises the technician, reviews prescriptions and performs his or her duties from a remote location via technology. Uses It is used in retail community pharmacy and outpatient/ discharge pharmacy settings, Telepharmacy gives patients convenient access to a pharmacist and prescription medication. Telepharmacy works to reduce readmission rates by improving patient adherence, helps improve financial performance and creates a better patient experience. 39

40. 3) IV admixture Definition The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) defines IV admixture as, ‘the preparation of pharmaceutical product which requires the measured addition of a medication to a 50ml or greater bag or bottle of intravenous fluid. ‘In layman’s terms, IV admixture is the mixture of IV solution administered to patients in a hospital setting. Uses Hospital pharmacies can save time and money by implementing Telepharmacy in the IV-admixture clean room. they save the time needed to suit up and enter the clean room to review the solution. Freeing up pharmacists time allows them to focus on clinical activities. 40

41. 4) Remote counseling Definition Remote- patient counseling equates to pharmacists providing patient counseling and interactive video session, or by some means through telecommunications. Uses Remote-patient counseling allows pharmacists to consult and provide a variety of pharmacy-care services to patients via secure, live video calls. Beyond being beneficial to retail independents, community, clinic and hospital-based pharmacies, remote counseling also provides opportunities for specialty counseling, discharge counseling and various clinical interactions with pharmacists. 41

42. Advantages: Improve efficiency (reduce work load) Improve accuracy (reduce errors) Improve documentation Enhance security(authorized access only) Reduce job stress and staff turnover Improve timeliness for medication delivery 42

43. Disadvantages: Complexity and function variation Requires additional staff training and technical help Downtime system failure and inflexibility Cost and space issues Automated medication dispensing devices: Small system -Pyxis medstation -Baxter ATC 212 dispensing system. -SCRIPT-PRO 200 Larger system -Baker cells -Baxter international 43

44. Bioelectric Medicines: Bioelectric medicine is an instrument, apparatus, implement, machine, implant , invitro reagent or other similar or related article, including a component part 44

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46. BIOSENSORS: It is a sensor that integrates a biological element with a physiochemical transducer to produce an electronic signal proportional to a single analyte which is then conveyed to a detector. 46

47. Components: 47

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49. Elements of biosensors: 49

50. Response Analysis Signal Detection Sample handling/preparation Analyte 50

51. Working principle: Analyte diffuses from the solution to the surface of the Biosensor. Analyte reacts specifically & efficiently with the Biological Component of the Biosensor. This reaction changes the physicochemical properties of the Transducer surface. This leads to a change in the optical/electronic properties of the Transducer Surface. The change in the optical/electronic properties is measured/ converted into electrical signal, which is detected. 51

52. Advantages: Highly Specific. Independent of Factors like stirring, pH, etc. Linear response, Tiny & Biocompatible. Easy to Use, Durable. Rapid, Accurate, Stable & Sterilizable. 52

53. Types: Based on bioreceptors: Enzyme biosensors Microbial biosensors Affinity biosensors Based on transduser: Potentiometric Amperometric Conductometric Optical Piezoelectric 53

54. Applications of Biosensors Food Analysis. Study of Biomolecules & their Interaction. Drug Development. Crime Detection. Medical Diagnosis (Clin & Lab). Environmental Field Monitoring. Quality Control. Industrial Process Control. Detection Systems for Biological Warfare Agents. Manufacture of Pharmaceuticals & Replacement organs. 54

55. REFERENCES U.S food and administration. Paving the way for personalized medicine. Kevin J Tracey ‘Molecular Mechanism of Bioelectrical Medicine. 3D printing technology in pharmaceutical drug delivery Three dimensional printing in pharmaceutics Personalized medicine-NCBI-NIH Science Direct; THE Faces of personalized medicine 55

56. THANK YOU 56