SR and CR

notes for dds

1. Noida Institute of Engineering and Technology (Pharmacy Institute) Greater Noida Sustained Release (SR) and Controlled Release (CR) Formulations Swarupanjali Padhi Asst. Professor(NIET Pharmacy Institute, Greater Noida) 10 December 2021 Unit: 1 Swarupanjali Padhi MPH102T Unit 1 DRUG DELIVERY SYSTEMS (MPH 102T) ( M Pharm 1 st Sem) 1

2. Course of Study for M. Pharm (Pharmaceutics) Semester - I Swarupanjali Padhi MPH102T Unit 1 10 December 2021 2

3. UNIT 1: Sustained Release (SR) and Controlled Release (CR) formulations: Introduction & basic concepts, advantages/disadvantages, factors influencing, physicochemical & biological approaches for SR/CR formulation, mechanism of drug delivery from SR/CR formulation. Polymers: Introduction, definition, classification, properties and application. Dosage forms for personalized medicine: Introduction, definition, pharmacogenetics, categories of patients for personalized medicines: Customized drug delivery systems, bioelectronic medicines, 3D printing of pharmaceuticals. Telepharmacy . Syllabus Swarupanjali Padhi MPH102T Unit 1 10 December 2021 3

4. Course Objectives Course Outcomes (COs) Programme Outcomes (POs) CO PO Mapping Prerequisite and Recap Introduction Sustained Release (SR) and Controlled Release (CR) formulations Polymers Dosage Forms for Personalized Medicine 10 December 2021 Content Swarupanjali Padhi MPH102T Unit 1 4

5. S ummary Daily Quiz Weekly Assignment MCQs Old Question Papers of AKTU Expected Questions for University Exam References and Books 10 December 2021 Content Swarupanjali Padhi MPH102T Unit 1 5

6. Upon completion of this unit the students will understand About various approaches to develop sustained release and controlled released drug delivery system. Design and develop novel drug delivery system using various types of polymer. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Course Objective 6

7. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Programme Outcomes (POs) Programme Outcomes (POs) Description PO1 An ability to independently carry out research /investigation and development work to solve practical problems PO2 An ability to write and present a substantial technical report/document PO3 Students should be able to demonstrate a degree of mastery over the area as per the specialization of the program. The mastery should be at a level higher than the requirements in the appropriate bachelor program 7

8. 8 Course Outcome CO Statement Level of Bloom Taxonomy The students will be able to - CO1 Design and develop novel drug delivery system L-3 and L-6 Swarupanjali Padhi MPH102T Unit 1 10 December 2021

9. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 CO PO MAPPING CO PO1 PO2 PO3 CO1 3 3 3 9

10. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Topic Wise Mapping with CO Unit Topic Mapping With CO1 Sustained Release (SR) and Controlled Release (CR) Formulations Sustained Release (SR) and Controlled Release (CR) Formulations 3 Polymer 3 Dosage Forms for Personalized Medicine 3 10

11. Topic:- Sustained Release (SR) and Controlled Release (CR) Formulations Objectives: the main objective of this topic are:- 1.Basics concept and definition, terminology used in the s ustained r elease (SR) and controlled r elease (CR) formulations 2. Its classification and release mechanism of s ustained release (SR) and controlled r elease (CR) formulations 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Topic Objective 11

12. Topic:- Polymer Objectives: the main objective of this topic are:- 1.Basics concept and definition of Polymer 2. Its classification and characteristics 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Topic Objective 12 Topic:- Dosage Forms for Personalized Medicine Objectives: the main objective of this topic are:- 1.Basics concept and definition of d osage forms for personalized medicine 2. Its classification and characteristics and different types of dosage forms for personalized medicine

13. B.Pharm (Industrial pharmacy ) 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Prerequisite and Recap 13

14. In this unit we will discuss on various physicochemical & biological approaches for SR/CR formulation SR/CR formulation are designed to continuously releasing medication over an extended period of time after administration of the single dose to get a prolonged therapeutic effect The aim of SR/CR preparation is to control the drug delivery to make certain the safety and increase efficacy of drug with improved patient compliance 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Introduction 14

15. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Sustained Release (SR) and Controlled Release (CR) formulations 15 Controlled drug delivery Delivers the drug at a predetermined rate, for locally or systemically, for a specified period. Sustained Release Dosage Form Designed to achieve a prolonged therapeutic effect by continuously releasing medication over an extended period of time usually (8-12 hours )after administration of the single dose. Basic concept of CR/SR

16. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Sustained Release (SR) and Controlled Release (CR) formulations 16 Controlled Release Programmed Release Timed release Repository Dosage Forms Alternative Expression Sustained Release Prolonged Release Extended Release Depot Formulations Alternative Expression of CR/SR

17. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Sustained Release (SR) and Controlled Release (CR) formulations 17 Differences Between Sustained and Controlled Drug Delivery System Sustained release dosage form Controlled release dosage form Provides medication over extended period of time Maintains constant drug levels in blood or tissue Generally do not attain zero order release kinetics (slow first order) Usually by releasing the drug in a zero-order pattern. Usually do not contain mechanisms to promote localization of the drug at active site. Controlled dosage forms contain methods to promote localization of the drug at active site.

18. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Sustained Release (SR) and Controlled Release (CR) formulations 18 Comparison of Drug Profile(1)

19. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Sustained Release (SR) and Controlled Release (CR) formulations 19 Drug Release Profile Zero Order Release: Delivery rate remains constant until device is exhausted of active agent. First Order Release: Release is directly proportional to amount of drug loaded in device. Higuchi model of release : release that is linear with reciprocal of square root of time.

20. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Sustained Release (SR) and Controlled Release (CR) formulations 20 Different Order Release Pattern(2)

21. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Sustained Release (SR) and Controlled Release (CR) formulations 21 Advantages of Sustained Release Dosage Forms Improved patient compliance Improved efficiency of treatment Better drug utilization Bio-availability of certain drugs can be increased Increased safety margin of high potency drugs and decreased local and systemic side effects Reduces nursing and hospitalization time

22. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Sustained Release (SR) and Controlled Release (CR) formulations 22 Disadvantages of Sustained Release Dosage Form Increased variability among dosage units Some of the drugs are not having any advantages if they are formulated in sustained release form The physicians having less flexibility in adjusting the dosage regimes( Lack of dosage flexibility ) Longer time to achieve therapeutic blood concentrations Increased variation in bioavailability Enhanced first-pass effect Dose-dumping Sustained concentration in overdose cases. Greater expense Need for additional patient education Eg : “Do not chew or crush the dosage form, swallow fully”

23. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Sustained Release (SR) and Controlled Release (CR) formulations 23 Factors to be Considered for Design Development path Medical rationale Biological factors Selection of drug candidate physico -chemical properties In vitro analysis formulation optimization In vivo data generation (BA / BE and / or CT) Discussion with regulatory authorities Data submission to regulatory authorities for marketing authorization / approval.

24. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 24 Medical Rationale Frequency of dosing Patient compliance Drug intake Fluctuation of serum concentration reduced side effect Sustained efficacy Sustained Release (SR) and Controlled Release (CR) formulations

25. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 25 Biological Factors Absorption Absorption Window Distribution Metabolism Dose Dependent Bio-Availability Drug -Protein Binding Therapeutic Index Duration of Action (Half – life) Margin of Safety (NTI – Digoxin ) Circadian Rhythm (ISMN, Theophylline , Nicotinic acid etc.) Sustained Release (SR) and Controlled Release (CR) formulations

26. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 26 Physico -Chemical Properties Molecular Size and Diffusivity Aqueous Solubility pKa - Ionization Constant Partition Coefficient Stability Protein Binding Sustained Release (SR) and Controlled Release (CR) formulations

27. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 27 Pharmacokinetic and Pharmacodynamic Considerations Dose Dumping First Pass metabolism Enzyme Induction/Inhibition upon multiple dosing Variability of urinary pH effect on drug elimination Prolonged drug absorption Variability in GI Empting and motility Sustained Release (SR) and Controlled Release (CR) formulations

28. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 28 Different Approaches for SR/CR Formulations: Chemical approach Biological approach Pharmaceutical approach Sustained Release (SR) and Controlled Release (CR) formulations

29. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 29 Chemical Approach: It involves alteration of physical/ chemical properties of the drug Complexation DC (solid) DC (solution) Absorption Ex: Drug+ ß- CycloDextrin Drug adsorbate Ad (solid) D Absorption Ex: acetaminophen+ glass adsorbate Prodrugs PD solid PD solution PD plasma Elimination Ex: Levodopa , Carbidopa . Sustained Release (SR) and Controlled Release (CR) formulations

30. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 30 Biological Approach Alteration of metabolic rate: carbidopa to prevent the metabolism of l- dopa Alteration of elimination rate: probencid to prevent tubular secretion of penicillin Sustained Release (SR) and Controlled Release (CR) formulations

31. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 31 Pharmaceutical Approach Dissolution controlled release system Drug polymer matrix formulation Encapsulation Diffusion controlled release system Reservoir device Matrix device Bio-erodible and combination of diffusion and dissolution system Ion- exchange resin-drug complex Sustained Release (SR) and Controlled Release (CR) formulations

32. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 32 Mechanism of Drug Delivery From SR/CR Formulation 1. Dissolution : Matrix Encapsulation 2. Diffusion : Matrix Reservoir 3. Combination of both dissolution & diffusion. 4. Osmotic pressure-controlled system Sustained Release (SR) and Controlled Release (CR) formulations

33. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 33 Dissolution Solid substances solubilizes in a given solvent. Mass transfer from solid to liquid. Rate determining step: Diffusion from solid to liquid. Several theories to explain dissolution – Diffusion layer theory (imp) Surface renewal theory Limited solvation theory. Sustained Release (SR) and Controlled Release (CR) formulations

34. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 34 Noyes Whitney Equation dc/dt = kD.A (Cs – C ) dc/dt = D/h A. (Cs – C) dc/dt = Dissolution rate, k= Dissolution rate constant (1st order). D = Diffusion coefficient/diffusivity Cs = Saturation/ maximum drug solubility. C = Conc. Of drug in bulk solution. Cs-C= concentration gradient. h =Thickness of diffusion layer Sustained Release (SR) and Controlled Release (CR) formulations

35. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 35 Matrix Type (3) Also called as Monolith dissolution controlled system. Controlled dissolution by: Altering porosity of tablet. Decreasing its wettebility . Dissolving at slower rate. First order drug release. Drug release determined by dissolution rate of polymer. Examples: Dimetane extencaps , Dimetapp extentabs . Sustained Release (SR) and Controlled Release (CR) formulations

36. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 36 Encapsulation(3) Called as Coating dissolution controlled system. Dissolution rate of coat depends upon stability & thickness of coating. Masks colour, odour, taste, minimising GI irritation. One of the microencapsulation method is used. coat Examples: Ornade spansules , Chlortrimeton Repetabs Sustained Release (SR) and Controlled Release (CR) formulations

37. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 37 Diffusion Major process for absorption. No energy required. Drug molecules diffuse from a region of higher concentration to lower concentration until equilibrium is attained. Directly proportional to the concentration gradient across the membrane. Sustained Release (SR) and Controlled Release (CR) formulations

38. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 38 Matrix Diffusion Types Rigid Matrix Diffusion Materials used are insoluble plastics such as PVP & fatty acids. Swellable Matrix Diffusion Also called as Glassy hydrogels. Popular for sustaining the release of highly water soluble drugs. Materials used are hydrophilic gums. Examples : Natural- Guar gum, Tragacanth . Semisynthetic -HPMC, CMC, Xanthum gum. Synthetic - Polyacrilamides . Examples: Glucotrol XL, Procardia XL Sustained Release (SR) and Controlled Release (CR) formulations

39. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 39 Matrix Diffusion Types(3) Sustained Release (SR) and Controlled Release (CR) formulations

40. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 40 Matrix System Higuchi Equation Q = DE/T (2A.E Cs)Cs.t)1/2 Where , Q=amt of drug release per unit surface area at time t. D=diffusion coefficient of drug in the release medium. E=porosity of matrix. Cs=solubility of drug in release medium. T=tortuosity of matrix. A=concentration of drug present in matrix per unit volume. Sustained Release (SR) and Controlled Release (CR) formulations

41. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 41 Reservoir System Also called as Laminated matrix device. Hollow system containing an inner core surrounded in water insoluble membrane. Polymer can be applied by coating or micro encapsulation. Rate controlling mechanism - partitioning into membrane with subsequent release into surrounding fluid by diffusion. Commonly used polymers - HPC, ethyl cellulose & polyvinyl acetate. Examples: Nico-400, Nitro-Bid Sustained Release (SR) and Controlled Release (CR) formulations

42. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 42 Reservoir System(3) Sustained Release (SR) and Controlled Release (CR) formulations

43. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 43 Dissolution & Diffusion Controlled Release System(3) Drug encased in a partially soluble membrane. Pores are created due to dissolution Insoluble membrane of parts of membrane. It permits entry of aqueous medium dissolution into core & drug dissolution. Diffusion of dissolved drug out of Drug system. Ex- Ethyl cellulose & PVP mixture Pore created by dissolves in water & create pores of dissolution of insoluble ethyl cellulose membrane. Sustained Release (SR) and Controlled Release (CR) formulations

44. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 44 Osmotic Pressure Controlled System Provides zero order release Drug may be osmotically active, or combined with an osmotically active salt (e.g., NaCl). Semipermeable membrane usually made from cellulose acetate. More suitable for hydrophilic drug. Examples: Glucotrol XL, Procardia XL Sustained Release (SR) and Controlled Release (CR) formulations

45. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 45 Osmotic Pressure Controlled System Equation (Q/t) z = Pw Am/ hm ( π s- π e ) (Q/t)= Rate of zero order drug release. Pw, Am & hm= water permeability, effective surface area & thickness of semipermeable membrane. π s= osmotic pressure of saturated solution of osmotically active drug or salt in system. π e = osmotic pressure of GI fluid Sustained Release (SR) and Controlled Release (CR) formulations

46. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 46 Osmotic Pressure Controlled System(3) Sustained Release (SR) and Controlled Release (CR) formulations

47. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 47 Osmotic Pressure Controlled System(3) Sustained Release (SR) and Controlled Release (CR) formulations

48. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Polymers 48 Polymers are long chain giant organic molecules are assembled from many smaller molecules called monomers. Polymers consist of many repeating monomer units in long chains. A polymer is analogous to a necklace made from many small beads (monomers) Definition of Polymer

49. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Polymers 49 Classification of Polymers(4)

50. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Polymers 50 Properties of Polymers The physical properties of a polymer, such as its strength and flexibility depend on: Chain length - in general, the longer the chains the stronger the polymer; Side groups - polar side groups give stronger attraction between polymer chains, making the polymer stronger; Branching - straight, unbranched chains can pack together more closely than highly branched chains, giving polymers that are more crystalline and therefore stronger; Cross-linking - if polymer chains are linked together extensively by covalent bonds, the polymer is harder and more difficult to melt.

51. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Polymers 51 Strength of Polymers In general, the longer the polymer chain, the stronger the polymer. There are two reasons for this Longer chains are more tangled There are more intermolecular forces between the chains because there are more points of contact.  These forces, however, are quite weak for polyethene. Areas in a polymer where the chains are closely packed in a regular way are said to be crystalline .  The percentage of crystallinity in a polymer is very important in determining its properties.  The more crystalline the polymer, the stronger and less flexible it becomes.

52. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Polymers 52 When a polymer is stretched (cold-drawn), a neck forms.  In the neck the polymer chains line up producing a more crystalline region.  Cold-drawing leads to an increase in strength. The first polyethene which was made contained many chains which were branched.  This resulted in a relatively disorganised structure of low strength and density.  This was called low density polyethene ( ldpe ) In the crystalline form, the methyl groups all have the same orientation along the chain.  This is called the isotactic form.  In the amorphous form, the methyl groups are randomly orientated.  This is called the atactic form. Polymers with a regula r structure are said to be stereoregular . Strength of Polymer

53. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Polymers 53 Application of Polymers(5)

54. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 54 Polymers

55. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 55 Polymers

56. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 56 Polymers

57. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 57 Polymers

58. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 58 Polymers

59. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 59 Polymers

60. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Polymers 60 Application of Polymers(6)

61. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Polymers 61 Application of Polymers(6)

62. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 62 Personalized Medicine(7) Introduction The concept of personalized medicine dates back many hundreds of years. Progresses in various field of chemistry, histochemistry and microscopy had enabled the technologists to begin to apprehend the underlying causes of disease. Sequencing of the human genome at the turn of the 21st century set in motion the transformation of personalized medicine from an idea to a practice

63. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 63 Personalized Medicine Definition The term “personalized medicine” is often described as providing “the right patient with the right drug at the right dose at the right time.” More broadly, “personalized medicine” may be thought of as the tailoring of medical treatment to the individual characteristics, needs and preferences of a patient during all stages of care, including prevention, diagnosis, treatment and follow-up. Other terms Precision medicine stratified medicine Targeted medicine pharmacogenomics

64. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 64 Personalized Medicine(7)

65. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 65 Personalized Medicine(8)

66. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 66 Pharmacogenetics The study of variations of DNA and RNA characteristics as related to drug responsive is a critically important area of personalized medicine Merging of developments in pharmacology and genomics Search for to comprehend how differences in genes and their expression affect the body’s response to medications. Uses genetic information (such as DNA sequence, gene expression, and copy number) for purposes of explaining interindividual differences in drug metabolism (pharmacokinetics) and physiological drug response (pharmacodynamics).

67. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 67 Pharmacogenomics(8)

68. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 68 Pharmacogenetics(8)

69. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 69 Pharmacogenetics(8)

70. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 70 Categories of Patients for Personalised Medicine: Patients are mainly classified depending upon the genetic polymorphism Cytochrome p450 genetic polymorphism. Different families of enzymes polymorphism

71. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 71 Customized Drug Delivery Systems Customized medicines is prepared based on each patient’s medical history, needs, genetics, health conditions and other factors. Different tools of Customized drug delivery systems Bioelectronic Medicines, 3D Printing of Pharmaceuticals. Telepharmacy .

72. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 72 Bioelectronic Medicines(9)

73. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 73 Bioelectronic Medicines(9)

74. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 74 3D Printing Technology (10) Current 3D printing technologies in pharmaceutical drug delivery: Inkjet printing Zip dose Thermal inkjet printing Fused deposition modeling

75. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 75 Three-dimensional (3D) printing is an additive manufacturing method, where successive layers of material are deposited or solidified to form a 3D structure. It uses computer aided drafting technology and programming to produce 3D object by layering material on to a substrate. A variety of 3D printing technologies have been developed to fabricate novel solid dosage forms, which are among the most renowned and distinct products today. The present review focussed on briefing various techniques, applications of 3D printing in pharmaceutical technology. Thermal Ink-Jet Printing In thermal inkjet printing, the aqueous ink fluid is converted to vapour form through heat and expands to push the ink drop out of a nozzle. 6 It is used in the preparation of drug-loaded biodegradable microspheres, drug-loaded liposomes 7, patterning microelectrode arrays coating and loading drug eluting stents. 8 It is also an efficient and practical method of producing films of biologics without compromising protein activity. Dosage Forms for Personalized Medicine

76. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 76 Dosage Forms for Personalized Medicine

77. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 77 Inkjet printing In this technique, the Ink is deposited onto a substrate either in the form of Continuous Inkjet printing (CIJ) or Drop on Demand (DoD) printing, hence it provides a high resolution printing capability15 (Table 2).Inkjet printing is also called as ‘mask-less’ or ‘tool-less’ approach because the formation of desired structure Dosage Forms for Personalized Medicine

78. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 78 mainly depends upon the movement of inkjet nozzle or movement of the substrate for an accurate and reproducible formation. It has a low processing cost, rapid processing rates, generation of minimal waste, it gives CAD information in a ‘direct write’ manner and it process material over large areas with minimal contamination Dosage Forms for Personalized Medicine

79. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 79 Fused deposition modelling (FDM) Fused deposition modelling (FDM) is commonly used technique in 3D printing, in which the materials are soften or melt by heat to create objects during printing (Fig 3),Hence there are several dosage forms listed in Table 3. FDM 3D printing helps in manufacturing delayed release printlets without an outer enteric coating, and also provides personalised dose medicines. FDM 3D printing however, indicates several limitations of the system such as lack of suitable polymers, slow and often incomplete drug release because the drug remain trapped in the polymers, and the miscibility of the drug and additives with the polymers used was not evaluate Fig 3: Fused deposition Dosage Forms for Personalized Medicine

80. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 80 Zip dose is the world’s first and only FDA-validated, commercial-scale 3DP in new therapeutic areas for drug manufacturers. (Fig 4) It has a unique digitally coded layering and zero-compression processes, which is used for formulating a tablet with high dose and rapid disintegration .Hence it helps in overcoming a difficulty in swallowing. 62 Spritam ® ( Antiepilipsey drug) is an orodispersible tablet, marketed by Aprecia Pharmaceuticals based on powder bed fusion by layer-by-layer production system. In which it consists of the active ingredient, excipients and a binder liquid to produce a matrix tablet. Dosage Forms for Personalized Medicine

81. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 81 Extrusion 3D printing In this technique the material is extruded from the automated nozzle on to the substrate and it does not require any higher support material. It is only used to fabricate tablet containing Guaifenesin as expectorant. The materials that can be extruded are molten polymers, suspensions, semisolids, pastes. Dosage Forms for Personalized Medicine

82. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 82 Hot melt extrusion (HME) Hot melt extrusion (HME) is the process of melting polymer and drug at high temperature and the pressure is applied in the instrument continuously for blending (Fig 6).It is a continuous manufacturing process that includes several operations such as feeding, heating, mixing and shaping. In recent years, it has proved that HME has the ability to improve the solubility and bioavailability of poorly soluble drugs Dosage Forms for Personalized Medicine

83. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 83 Stereolithography Stereolithography is the technique in which a computer controlled laser beam is used to solidify the liquid polymer or resin, thereby creating a 3D structure89 (Fig 7).SLA has some advantages over other types of 3DP, mainly it’s remarkable resolution and the avoidance of thermal processes can be detrimental for certain drug molecules. 90 Some of the drugs prepared by Stereolithography are given in Table 7. Dosage Forms for Personalized Medicine

84. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 84 3D Printing Technology (9)

85. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Dosage Forms for Personalized Medicine 85 Use of electronic information and communication technologies to provide pharmaceutical care when distance separates the pharmacist and the patient. Telepharmacy often includes electronic health record integration,audio -video connections, and increased patient access to pharmaceutical care Telepharmacy (11)

86. Youtube /other Video Links 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 86 Faculty Video Links/ Youtube & NPTEL Video Links and Online Courses Details (if any) https://www.youtube.com/watch?v=jJ2GyH2AKtA

87. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Summary This unit covers the Basics of controlled and sustained release dosages forms The various physico -chemical and biological factors affecting SR/CR drug delivery system Definition, properties and application of polymers Concepts of personalized medicine 87

88. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Daily Quiz Sl No. Question 1. What are the different type of 3D printer used in drug delivery system? 2. State the different properties of proteins. 3. State the different biological factors to be considered for SR/CR formulation. 4. Enlist the various classification of polymer. 5. What is pharmacogenetics? 6. Differentiate between controlled release and sustained release. 7 Differentiate between pharmacogenetics and pharmacogenomics. 88

89. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Weekly Assignment Sl No Question 1. Describe the biosensors. 2. Write note on telepharmacy . 3. Describe mechanism of drug delivery from SR/CR formulation. 4. Write a brief note on Polymers 5 Describe the personalized medicine. 89

90. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 MCQ s 1.Controlled release follows………………………. Kinetics. First order Zero order Second order None Q.2. Which one of the following is NOT true? Mass and density a.Drug release from reservoir systems is controlled by diffusion b) Drug release from matrix systems is controlled by diffusion c) Drug release from reservoir systems normally follow zero-order kinetics d) Drug release from matrix systems normally follow zero-order kinetics Q.3. When the release of drug from a dosage form satisfies Higuchi’s equation, the release of drug can be considered as Absorption rate controlled Diffusion rate controlled Dissolution rate controlled Dosing rate controlled Q.4. A matrix type diffusion sustained release dosage for fits which kinetic model Higuchi model first zero second 90

91. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 MCQ s Q.5. Current 3D printing technologies in pharmaceutical drug delivery a. Inkjet printing b Zip dose c. Thermal inkjet printing d. All of the above Q.6. Different tools of Customized drug delivery systems a. Bioelectronic Medicines, b. 3D Printing of Pharmaceuticals. c.Telepharmacy . d. All of the above Q.7. Strength of polymer depends on Chain length Branching Crosslinkings All of the above 91

92. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Old Question Papers of AKTU 92

93. Q1. Describe 3D printing in personalized medicine Q2.Write the classification, properties and application of polymer. Q3. Explain in detail the mechanism of drug release. Q4. Enumerate the various physicochemical & biological approaches for SR/CR formulation. Q5. Describe in detail about the bioelectronic medicines. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Expected Questions for University Exam 93

94. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 References and Books to be followed Text Books: Controlled Drug Delivery Systems by Robinson, J. R., Lee V. H. L, Marcel Dekker,Inc ., New York, 1992. Chichester and Weinheim Encyclopedia of controlled delivery, Editor- Edith Mathiowitz , Published by WileyInterscience Publication, John Wiley and Sons, Inc, New York! Chichester/Weinheim. Controlled and Novel Drug Delivery by Jain, N.K. CBS Publishers & Distributors, New Delhi, First edition 1997 (reprint in 2001). Controlled Drug Delivery - concepts and advances by Vyas S.P. and Khar , R.K. Vallabh Prakashan , New Delhi, First edition 2002. 94 References https://www.slideshare.net/IreneDaniel8/personalized-medicine-ppt

95. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 References and Books to be followed References for Figures https://www.slideshare.net/PrinceDivyesh/controlled-and-sustained-release-dosage-formcontrolled-release-dosage-formsuistained-release-dosage-form http://www.authorstream.com/Presentation/v.ramani007-1635467-ch-1-controlled-sustained-release-dosage-forms/ https://www.slideshare.net/gaurav11288/controlled-release-oral-drug-delivery https://www.slideshare.net/janhavizope/polymers-47362631 https://www.slideshare.net/RonakkB17/polymer-in-pharmacy-and-application-of-polymers https://www.slideshare.net/suraiyaoyshe/polymers-final3 https://blog.crownbio.com/pdx-personalized-medicine https://www.slideshare.net/micheldumontier/personalized-medicine-5853949 https://www.slideshare.net/SachinG19/personalized-medicines-176733523 https://www.sciencedirect.com/science/article/pii/S1818087618307852 https://yrf.ipsf.org/d/27-telepharmacy 95

96. 10 December 2021 Swarupanjali Padhi MPH102T Unit 1 Noida Institute of Engineering and Technology (Pharmacy Institute) Greater Noida Thank You!!!!!!!!!! 96