The document discusses forced degradation studies which are used to assess the stability of drug substances and products and develop stability indicating analytical methods. Forced degradation involves subjecting drug samples to extreme chemical and environmental conditions to purposefully degrade the drug. This helps identify possible degradation pathways and products. The document outlines experimental designs for forced degradation studies on both solid and solution drug substances involving heat, humidity, light, acid/base hydrolysis, and oxidation. It emphasizes the need for appropriate forced degradation studies to develop stability indicating analytical methods.
Dissolution considerations for novel immediate release formulationsstudent
1. Dissolution testing is an important test for assessing the in vivo performance of immediate release dosage forms. It can be used for quality control as well as predicting in vivo drug release.
2. The choice of dissolution medium depends on the Biopharmaceutics Classification System class of the drug. Simple media like SGF can be used for Class 1 drugs while biorelevant media like FaSSIF and FeSSIF are needed for Class 2 drugs.
3. Factors like drug solubility, permeability, dosage form properties and test conditions need to be considered when designing a dissolution test in order to obtain a discriminating and meaningful test.
TESTS ON FORMULATIONS: Content Uniformity, Hardness, Dissolution.Amruta Sonawane
This document summarizes key tests performed on pharmaceutical formulations, including content uniformity, hardness, and dissolution. Content uniformity testing ensures each tablet contains the intended amount of active drug with little variation between tablets. Hardness testing measures a tablet's crushing strength, with limits varying based on the type of tablet. Dissolution testing predicts in vivo drug release profiles using basket or paddle apparatus under set conditions to simulate gastrointestinal fluids. These tests help ensure consistent dosing, sufficient strength, and controlled drug release.
COMPARATIVE EVALUATION OF DIFFERENT PARACETAMOL BRANDSShikha Popali
THE PARACETAMOL TABLETS IS COMMONLY TAKEN AND PRESCRIBED FOR FEVER , SO HERE WE HAVE MADE PRACTICAL IS IT TRUE EVALUATION LABEL AND WHICH BRAND IS MORE SAFE.
The document summarizes key information about Juvederm XC, a hyaluronic acid dermal filler. It has three main points:
1) Juvederm XC contains lidocaine, which clinical studies show provides a more comfortable patient experience compared to Juvederm without lidocaine. Over 90% of patients reported less pain with Juvederm XC.
2) The addition of lidocaine does not impact the chemical or physical properties of Juvederm. Clinical trials found Juvederm XC to be as effective and safe as Juvederm without lidocaine, with the exception of less pain and tenderness.
3
Preformulation Studies by Jayesh Anil MahirraoJayesh Mahirrao
The presentation contains the relevant information about the Preformulation Studies done for the pharmaceutical dosage form. It can be useful specially to the students pursuing graduation and post-graduation in pharmacy. It is prepared on the basis of PCI syllabus of M. Pharm. (Pharma Technology and Pharmaceutics).
The document discusses the classification and properties of matter. It defines pure substances as elements and compounds, which have a fixed composition, while mixtures can have varying compositions. Mixtures are classified as homogeneous if the parts are evenly distributed or heterogeneous if they are noticeably separated. The document also examines physical properties like density, hardness, and melting point. It reviews separation methods like filtration and distillation, and defines chemical properties like reactivity and flammability.
Work sample: Starbucks Store Brand Threat AnalysisBinglinglin
Evaluate the nature and severity of store brand/ private label threat against Startbucks within premium package coffee category in four major retailers - Kroger, Target, Safeway and Publix, and uncover the reason for customers to switch from Starbucks to Store Brand.
The document discusses forced degradation studies which are used to assess the stability of drug substances and products and develop stability indicating analytical methods. Forced degradation involves subjecting drug samples to extreme chemical and environmental conditions to purposefully degrade the drug. This helps identify possible degradation pathways and products. The document outlines experimental designs for forced degradation studies on both solid and solution drug substances involving heat, humidity, light, acid/base hydrolysis, and oxidation. It emphasizes the need for appropriate forced degradation studies to develop stability indicating analytical methods.
Dissolution considerations for novel immediate release formulationsstudent
1. Dissolution testing is an important test for assessing the in vivo performance of immediate release dosage forms. It can be used for quality control as well as predicting in vivo drug release.
2. The choice of dissolution medium depends on the Biopharmaceutics Classification System class of the drug. Simple media like SGF can be used for Class 1 drugs while biorelevant media like FaSSIF and FeSSIF are needed for Class 2 drugs.
3. Factors like drug solubility, permeability, dosage form properties and test conditions need to be considered when designing a dissolution test in order to obtain a discriminating and meaningful test.
TESTS ON FORMULATIONS: Content Uniformity, Hardness, Dissolution.Amruta Sonawane
This document summarizes key tests performed on pharmaceutical formulations, including content uniformity, hardness, and dissolution. Content uniformity testing ensures each tablet contains the intended amount of active drug with little variation between tablets. Hardness testing measures a tablet's crushing strength, with limits varying based on the type of tablet. Dissolution testing predicts in vivo drug release profiles using basket or paddle apparatus under set conditions to simulate gastrointestinal fluids. These tests help ensure consistent dosing, sufficient strength, and controlled drug release.
COMPARATIVE EVALUATION OF DIFFERENT PARACETAMOL BRANDSShikha Popali
THE PARACETAMOL TABLETS IS COMMONLY TAKEN AND PRESCRIBED FOR FEVER , SO HERE WE HAVE MADE PRACTICAL IS IT TRUE EVALUATION LABEL AND WHICH BRAND IS MORE SAFE.
The document summarizes key information about Juvederm XC, a hyaluronic acid dermal filler. It has three main points:
1) Juvederm XC contains lidocaine, which clinical studies show provides a more comfortable patient experience compared to Juvederm without lidocaine. Over 90% of patients reported less pain with Juvederm XC.
2) The addition of lidocaine does not impact the chemical or physical properties of Juvederm. Clinical trials found Juvederm XC to be as effective and safe as Juvederm without lidocaine, with the exception of less pain and tenderness.
3
Preformulation Studies by Jayesh Anil MahirraoJayesh Mahirrao
The presentation contains the relevant information about the Preformulation Studies done for the pharmaceutical dosage form. It can be useful specially to the students pursuing graduation and post-graduation in pharmacy. It is prepared on the basis of PCI syllabus of M. Pharm. (Pharma Technology and Pharmaceutics).
The document discusses the classification and properties of matter. It defines pure substances as elements and compounds, which have a fixed composition, while mixtures can have varying compositions. Mixtures are classified as homogeneous if the parts are evenly distributed or heterogeneous if they are noticeably separated. The document also examines physical properties like density, hardness, and melting point. It reviews separation methods like filtration and distillation, and defines chemical properties like reactivity and flammability.
Work sample: Starbucks Store Brand Threat AnalysisBinglinglin
Evaluate the nature and severity of store brand/ private label threat against Startbucks within premium package coffee category in four major retailers - Kroger, Target, Safeway and Publix, and uncover the reason for customers to switch from Starbucks to Store Brand.
Decreasing Time-to-Market via Synchrotron Utilization to Discover Stable Form...Simon Curtis
Decreasing Time-to-Market via Synchrotron Utilization to Discover Stable Formulation from Steve Byrn & Pam Smith at Purdue University / Improved Pharma. This presentation focuses on finding solid forms to increase exposure, synchotron, amorphous complexes, predict/anticipate stability and synchotron / sameness and problem solving. Pam and Steve delivered this talk at the 2018 Controlled & Modified Drug Release Summit.
Oral Drug Formulation Innovations 2014Simon Curtis
The Oral Drug Formulation Innovations Summit will examine and showcase the industry's latest formulation and delivery technologies for enhancing solubility and maximizing bioavailability. Leading global formulation experts in both industry and academia will share unique strategies on how to effectively develop poorly soluble drugs into scientifically unique, compliant, patient-centric formulations. Additionally, innovative strategies to significantly reduce product development timelines will be shared, and the latest regulatory requirements will be discussed.
Applications of Modified Release during the Preclinical Stage - Weijia Zheng,...Simon Curtis
Dr. Wejia Zheng from AstraZeneca delivered a talk on Applications of Modified Release during the Preclinical Stage, this past May at the Controlled & Modified Drug Release Conference in Philadelphia, PA. The talk focused on the importance of modified release at the preclinical stage, common challenges, approaches to achieve modified release (routes of administration, formulation approaches, devices etc) and conclusions as well as examples.
This document discusses pharmaceutical solid forms, including polymorphs, hydrates, solvates, salts, co-crystals, and amorphous forms. It covers the impact of solid form on properties like solubility, stability, and processing. The document also discusses solid form screening, characterization, and selection methods to develop solid forms that balance solubility, stability, and manufacturability for drug products. Thermodynamics concepts like Gibbs free energy, enthalpy, and entropy are applied to explain relative stability of different solid forms.
The document discusses different types of solid forms that active pharmaceutical ingredients can take, including polymorphs, solvates, hydrates, salts, co-crystals, and the amorphous form. It notes that over 80% of pharmaceutical solids exhibit polymorphism. The thermodynamically most stable polymorph is generally preferred for stability reasons, though a metastable polymorph may be developed to provide a balance between processability and stability. Hydrates and solvates are discussed, with hydrates being the most common type of solvate. Salt and co-crystal formation can impact properties like dissolution and stability. The amorphous form lacks long-range order.
This document discusses pharmaceutical solid forms, including polymorphs, hydrates, solvates, salts, co-crystals, and amorphous forms. It covers the impact of solid form on properties like solubility, stability, and processing. The document also discusses solid form screening, characterization, and selection methods to develop solid forms that balance solubility, stability, and manufacturability for drug products. Thermodynamics concepts like Gibbs free energy, enthalpy, and entropy are applied to explain relative stability of different solid forms.
Formulations in drug discovery, changing the formulation paradigm in early drug discovery, critical role of solubility and formulation screening, innovative formulation screening with low amounts of test compound and the impact of early formulation screening on pharmacokinetic studies from Suma Gopinathan at Lexicon Pharmaceuticals.
Solubilities of Crystalline Drugs in Polymers: An Improved Analytical Method ...Simon Curtis
Solubilities of Crystalline Drugs in Polymers: An Improved Analytical Method and Comparison of Solubilities of Indomethacin and Nifedipine in PVP, PVP/VA, and PVAc - YE SUN,1 JING TAO,1 GEOFF G. Z. ZHANG,2 LIAN YU1
This document summarizes literature on cocrystal systems published in 2011 that are of interest to pharmaceutical scientists. It begins with an introduction to cocrystal systems and relevant review articles. It then discusses general articles on cocrystal engineering principles and characterization methods. The majority of the document summarizes literature on preparation methods for cocrystal systems and specific pharmaceutical cocrystal systems that were reported. It concludes with a discussion of regulatory guidance on pharmaceutical cocrystals.
Decreasing Time-to-Market via Synchrotron Utilization to Discover Stable Form...Simon Curtis
Decreasing Time-to-Market via Synchrotron Utilization to Discover Stable Formulation from Steve Byrn & Pam Smith at Purdue University / Improved Pharma. This presentation focuses on finding solid forms to increase exposure, synchotron, amorphous complexes, predict/anticipate stability and synchotron / sameness and problem solving. Pam and Steve delivered this talk at the 2018 Controlled & Modified Drug Release Summit.
Oral Drug Formulation Innovations 2014Simon Curtis
The Oral Drug Formulation Innovations Summit will examine and showcase the industry's latest formulation and delivery technologies for enhancing solubility and maximizing bioavailability. Leading global formulation experts in both industry and academia will share unique strategies on how to effectively develop poorly soluble drugs into scientifically unique, compliant, patient-centric formulations. Additionally, innovative strategies to significantly reduce product development timelines will be shared, and the latest regulatory requirements will be discussed.
Applications of Modified Release during the Preclinical Stage - Weijia Zheng,...Simon Curtis
Dr. Wejia Zheng from AstraZeneca delivered a talk on Applications of Modified Release during the Preclinical Stage, this past May at the Controlled & Modified Drug Release Conference in Philadelphia, PA. The talk focused on the importance of modified release at the preclinical stage, common challenges, approaches to achieve modified release (routes of administration, formulation approaches, devices etc) and conclusions as well as examples.
This document discusses pharmaceutical solid forms, including polymorphs, hydrates, solvates, salts, co-crystals, and amorphous forms. It covers the impact of solid form on properties like solubility, stability, and processing. The document also discusses solid form screening, characterization, and selection methods to develop solid forms that balance solubility, stability, and manufacturability for drug products. Thermodynamics concepts like Gibbs free energy, enthalpy, and entropy are applied to explain relative stability of different solid forms.
The document discusses different types of solid forms that active pharmaceutical ingredients can take, including polymorphs, solvates, hydrates, salts, co-crystals, and the amorphous form. It notes that over 80% of pharmaceutical solids exhibit polymorphism. The thermodynamically most stable polymorph is generally preferred for stability reasons, though a metastable polymorph may be developed to provide a balance between processability and stability. Hydrates and solvates are discussed, with hydrates being the most common type of solvate. Salt and co-crystal formation can impact properties like dissolution and stability. The amorphous form lacks long-range order.
This document discusses pharmaceutical solid forms, including polymorphs, hydrates, solvates, salts, co-crystals, and amorphous forms. It covers the impact of solid form on properties like solubility, stability, and processing. The document also discusses solid form screening, characterization, and selection methods to develop solid forms that balance solubility, stability, and manufacturability for drug products. Thermodynamics concepts like Gibbs free energy, enthalpy, and entropy are applied to explain relative stability of different solid forms.
Formulations in drug discovery, changing the formulation paradigm in early drug discovery, critical role of solubility and formulation screening, innovative formulation screening with low amounts of test compound and the impact of early formulation screening on pharmacokinetic studies from Suma Gopinathan at Lexicon Pharmaceuticals.
Solubilities of Crystalline Drugs in Polymers: An Improved Analytical Method ...Simon Curtis
Solubilities of Crystalline Drugs in Polymers: An Improved Analytical Method and Comparison of Solubilities of Indomethacin and Nifedipine in PVP, PVP/VA, and PVAc - YE SUN,1 JING TAO,1 GEOFF G. Z. ZHANG,2 LIAN YU1
This document summarizes literature on cocrystal systems published in 2011 that are of interest to pharmaceutical scientists. It begins with an introduction to cocrystal systems and relevant review articles. It then discusses general articles on cocrystal engineering principles and characterization methods. The majority of the document summarizes literature on preparation methods for cocrystal systems and specific pharmaceutical cocrystal systems that were reported. It concludes with a discussion of regulatory guidance on pharmaceutical cocrystals.
Amorphous Solid Dispersions: Application Of Spray Drying Formulations For Dis...
Expediting Time-to-Market and Reducing Time-to-Launch with Physicochemical Optimization
1. Expediting Time-to-Market and
Reducing Time-to-Launch with
Physicochemical Optimization
Stephen R. Byrn
Purdue University and Improved Pharma, LLC
West Lafayette, Indiana
1
2. Outline
Effectively selecting the correct form and correct salt of
your drug substance
Examining key strategies for managing solubility in lead
optimization
Evaluating physicochemical properties, generating an
understanding of the material’s stability under various
conditions, leading to selecting the optimal drug delivery
system
Achieving the right balance between efficacy,
patentability concerns, toxicity, and ADME properties for
your compound
2
3. Outline
Effectively selecting the correct form and correct salt of
your drug substance
Examining key strategies for managing solubility in lead
optimization
Evaluating physicochemical properties, generating an
understanding of the material’s stability under various
conditions, leading to selecting the optimal drug delivery
system
Achieving the right balance between efficacy,
patentability concerns, toxicity, and ADME properties for
your compound
3
4. Overall Considerations in Selecting the
Correct Form
Bio- Mechanical
Solid State Stability
pharmaceutics Properties
Formulation Design &
Product Design
(Dosage Form Design)
Process Design
4
5. Workflow for Merck Strategy
Michael Palucki, John D. Higgins, Elizabeth Kwong, and
Allen C. Templeton, J. Med. Chem., 53, 5897 (2010)
5
6. Only a Short Time to Select the Form in
Year 1
Major Focus
Matest
of SSC
10. Development Strategy with Polymorph Screening
– 8 Weeks
Week 1 Week 4 Week 5 Week 8
Solubility Is drug Yes Select Formulation Solubility
Study soluble? Polymorph Screen Form Screen Dissolution
Rat PK
No
Stress Testing
Can it Yes Select Salt Polymorph Select Formulation Solubility
form salts? Salt Screen Form Screen Form Screen Dissolution
Rat PK
Optional
Stress Testing
No Milling Study
Select Solubility
Amorphous Dispersion Screen Form Dissolution
Rat PK
Optional
Stress Testing
Crystallization
Inhibitor Screen
Select Solubility
Vehicle Screen Veh. Dissolution
Rat PK
Stress Testing
10
11. Development Strategy First 4 weeks
Week 1 Week 4
Solubility Is drug Yes
Study soluble? Polymorph Screen
No
Can it Yes Select
form salts? Salt Screen Form
No
Amorphous Dispersion Screen
Vehicle Screen
11
12. Strategy
Optimize form and formulation early
Merck Review in J. Med. Chem. Present similar strategy – see Higgins et al., Michael Palucki, John D.
Higgins, Elizabeth Kwong, and Allen C. Templeton, J. Med. Chem., 53, 5897 (2010)
Find best form within 12 weeks for toxicology
and first in human clinical trials
Utilize acoustic levitation method to facilitate
early formulation development
12
13. Acoustic Levitation – A Frist Step in
Finding the Right Form
Finding best form
Very small amounts of material
One day study
Can apply Taylor method to determine if the
compound is a fast crystallizer
Simulates spray drying
13
19. Nanoparticles
Screen for nanoparticles in the case of fast
crystallization
Wet mill stable polymorph
Utilize Liversidge screen for crystal growth
inhibitors – US Patent 5,145,684
19
20. Salt Properties
CH3 OH
CO2 H3N
OH
H3CO HO
NSAID
compound melting percent weight aqueous solubility aqueous dissolution rate
point (ºC) gain at 81% RH (mg/mL) at pH3 (mg/min/cm2)
naproxen 160 0 0.016 ≤0.005
Na salt 267 21 178 21
THAM salt 191 0 11 1.0
Gu, L.; Strickley, R. G. Pharmaceutical Research 1987, 4, 255
21. Three Tier Salt Selection - Morris
Tier 1 Hygroscopicity
(7 Salts)
Tier 2 Solubility Crystal Changes
(4 salts)
Tier 3 Stability and Compatibility
22. DSC Curves for the
Calcium Salt of BMS 180431
5%RH
70%RH
26. Outline
Effectively selecting the correct form and correct salt of
your drug substance
Examining key strategies for managing solubility in lead
optimization
Evaluating physicochemical properties, generating an
understanding of the material’s stability under various
conditions, leading to selecting the optimal drug delivery
system
Achieving the right balance between efficacy,
patentability concerns, toxicity, and ADME properties for
your compound
26
27. Dissolution Studies of Formulations (50 mg
drug formulation in capsule)- in situ probe
27
28. Three Tier Salt Selection
Tier 1 Hygroscopicity
(7 Salts)
Tier 2 Solubility Crystal Changes
(4 salts)
Tier 3 Stability and Compatibility
29. DSC Curves for the
Calcium Salt of BMS 180431
5%RH
70%RH
31. Equilibrium Solubilities of BMS
180431 Salts in Water and 0.01M HCl
Salts Distilled Water 0.01M HCl
Solubility** Solubility*
(mg/mL) (mg/mL)
Calcium 2.8 0.67
Magnesium 3.7 0.65
Lysine >100 0.64
Arginine >100 0.61
* 25°C; µ = 0.1
** Solubilities are expressed in terms of free acid concentration
32. Outline
Effectively selecting the correct form and correct salt of
your drug substance
Examining key strategies for managing solubility in lead
optimization
Evaluating physicochemical properties, generating an
understanding of the material’s stability under various
conditions, leading to selecting the optimal drug delivery
system
Achieving the right balance between efficacy,
patentability concerns, toxicity, and ADME properties for
your compound
32
33. Solid Dispersion – Spring and
Parachute Concept
J. Brouwers, Brewster et
al J Pharm Sci (2009)
98: 2549-2572
33
33
35. In vivo Exposure
Beagle Dog, 5 x increase in exposure
Friesen, D.T. et al
Mol Pharm
35 5 (2008) 1003-1019
36. Outline
Effectively selecting the correct form and correct salt of
your drug substance
Examining key strategies for managing solubility in lead
optimization
Evaluating physicochemical properties, generating an
understanding of the material’s stability under various
conditions, leading to selecting the optimal drug delivery
system
Achieving the right balance between efficacy,
patentability concerns, toxicity, and ADME properties for
your compound
36
37. Itraconazole Blood Levels in Pigs
80
Concentration itraconazole (ng/ml)
70
60 average sporanox
50
40 average itra 100mg
30
20 average Itra HPMC
10 300mg
0
average itra HPMCP
12
16
24
36
42
48
31.3
0
1
2
4
8
0.5
Time (h)
38. Dissolution Rates – An IVIVC
ITR Dispersions with Controls
Dissolution - USP I (Basket)
100 Media (0.1N HCl, 0.5%CTAB), 50rpm(1hr), 250rpm
90
80
70
% Drug Release
60
50
40
30
Sporanox 100mg
20 ITR HPMCP55(1:2) 300mg
10 ITR HPMC(1:2) 300mg
ITR Crystalline 100mg
0
0 500 1000 1500 2000 2500 3000
Time (min)
39. Improved Pharma Strategy for Fast
Development – 1 Year to IND
Improved Pharma is a Virtual Company
CRO Strategy – IP Belongs to Contractor
Merck approach
Michael Palucki, John D. Higgins, Elizabeth Kwong, and Allen C. Templeton, J. Med. Chem., 53, 5897 (2010)
Best in Class, US Subcontractors/Performance Sites
Argonne National Labs
SSCI, an Aptuit Company
Purdue University
A specific strategy, flow chart, timeline and plan
developed for each compound
39
40. Improved Pharma Services
Chemical synthesis Stability & Consistency
Solid state chemistry Quality by design
Preclinical/Toxicology Validated methods
IND Regulatory issues
Clinical Trials Intellectual Property
41. Intellectual Property
Include best method of making cocrystals-
salts-polymorphs (amorphous forms)-
nanocrystals
Patent form and formulation
Be sure to have claims that describe your
invention is various ways and with various
degrees of specificity.
41
43. Conclusion
Effectively selecting the correct form and correct salt
of your drug substance
Examining key strategies for managing solubility in
lead optimization
Evaluating physicochemical properties, generating
an understanding of the material’s stability under
various conditions, leading to selecting the optimal
drug delivery system
Achieving the right balance between efficacy,
patentability concerns, toxicity, and ADME
properties for your compound
43