Excipients..different types of excipients and its applications in pharmacetical industry for manufacturing of dosage forms.
few examples of commercially available excipients in the market for the manufacturing purpose of intended dosage forms.
Presentation about dissolution apparatus testing machine for tablet and new version which is manufactured by lab 8 "Industrial Pharmacy Course" faculty of pharmacy october 6 university.
we added new modification which is already applied and others not applied due to high cost but suggested.
and all modifications are approved from industrial pharmacy department O6U.
SOLID DISPERSION
Definition: The technology is the science of dispersing one or more active ingredients in an inert matrix in the solid stage.
Need of solid dispersion:
Increases Oral bioavailability of a drug
Increased dissolution rate.
Enhanced release of drugs from ointment.
Improved the solubility & stability.
The concept of solid dispersion was originally proposed by Sekiguchi & obi.
Increasing the dissolution, absorption & therapeutic efficacy of drugs in dosage forms.
Increasing solubility in water.
Improving the oral absorption and bioavailability of BCS Class II drugs.
Excipients..different types of excipients and its applications in pharmacetical industry for manufacturing of dosage forms.
few examples of commercially available excipients in the market for the manufacturing purpose of intended dosage forms.
Presentation about dissolution apparatus testing machine for tablet and new version which is manufactured by lab 8 "Industrial Pharmacy Course" faculty of pharmacy october 6 university.
we added new modification which is already applied and others not applied due to high cost but suggested.
and all modifications are approved from industrial pharmacy department O6U.
SOLID DISPERSION
Definition: The technology is the science of dispersing one or more active ingredients in an inert matrix in the solid stage.
Need of solid dispersion:
Increases Oral bioavailability of a drug
Increased dissolution rate.
Enhanced release of drugs from ointment.
Improved the solubility & stability.
The concept of solid dispersion was originally proposed by Sekiguchi & obi.
Increasing the dissolution, absorption & therapeutic efficacy of drugs in dosage forms.
Increasing solubility in water.
Improving the oral absorption and bioavailability of BCS Class II drugs.
This slide contains the preformulation studies.It contains the various physicochemical properties that must be undergo to formulate the better absorption and stabiity of the different type of dosage form.This is ultimately used for the B Pharmacy final year students.Download the colourful ppt and enjoy the experience.
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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.
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
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
2. Presentation Outline
• Challenges in Discovery toxicology formulation
development
• General concept of spray dried amorphous solid
dispersions
• Integration of spray drying technology in Discovery space
• Case studies of applications of amorphous solid dispersion
for Discovery toxicology studies
• Summary
• Acknowledgement
2
3. Challenges In Discovery Toxicology Formulation
Development
• Requirement of higher oral exposure (except for oncology
programs) to ensure safety margin:
– Exposures can be limited by
• Compound specific properties:
– Solubility can be significantly improved
– Dissolution rate by formulation strategies
– Permeability
– GI tract stability
– First pass effect
• Formulation specific properties:
– Maximum feasible dose: limited by feasible concentration,
dosing volume and daily allowed amount of excipients
– Release rate
3
4. Challenges In Discovery Toxicology Formulation
Development (continued)
• Prefer solution/suspension formulation
– Easiness for dosing especially for rodent species
– Easiness for body weight adjustment
– Besides bioperformance, need to address:
• Dosability:
– uniformity, viscosity and syringability
• Stability:
– Physical stability: polymorphism, disproportionation, particle size
distribution, pH shift, agglomeration and gelling
– Chemical stability: chemical degradation (hydrolysis, oxidation,
compatibility with excipients and photostability)
4
5. Challenges In Discovery Toxicology Formulation
Development (continued)
• Narrower choices of excipients
– To ensure clear read out of toxicity caused by API.
– Excipients with similar toxicity concern as the API have to be avoided.
– Wider choices for short term study. However, line of sight for long term
toxicology study is critical.
– Full knowledge of species specific toxicity of excipients is essential.
– Maximum daily allowed amount of excipients has to be established.
– Concern specific to the therapeutic area:
• Example: using lipid based formulations for lipid modifying agents
• Short development time for toxicology formulations
• Limited availability of API
5
6. Toxicology Formulation Strategies
• Solubilization
– Ionization by pH adjustment
– Salt
– Cosolvent
– Surfactant
– Complexation
– Lipid based formulation
• Increase dissolution rate through particle size reduction
– Micronization
– Nanoparticle
• Improve solubility by converting API to amorphous state and
maintaining it at amorphous state (amorphous solid
dispersion)
– Hot melt extrusion or melt quenching techniques
– Spray drying
6
7. Spray Drying Process
Atomization Spray
Gas Hot
Solution Credit: Galen Shi
Processing Gas Cool Evaporation
of Solvent
Spray
Droplet
Heat in
Hotter
region
Cooler
region Spray Dried Drug/Polymer
• Mix up liquid feed containing drug, polymer, and optional surfactants in a solution or suspension.
• Atomize liquid feed to generate desired droplet formation
• Dry droplets (fast drying rate) to generate amorphous, solid particles (from solution)
• Collect product from processing gas stream (e.g cyclone & bag filter)
7
8. How Spray Dried Amorphous Solid Enhances Drug
Exposure
Free Energy Solvated Drug G
G
Amorphous Drug
Crystalline Drug
• Amorphous state has higher free-energy No crystal lattice to break
Higher Thermodynamic Solubility
• Fine particle size Large surface area Improved Kinetic Dissolution
Amorphous solid dispersion is particularly useful for
compounds with high crystal lattice energy
8
9. Polymer Excipients in Spray Drying
Free Energy Amorphous Drug
Amorphous Drug
w/Polymer Better Solubility
Low Stability
Better Solubility Crystalline Drug
Better Stability
Poor Solubility Patrick Marsac with permission
Stable
•Polymers stabilize the
amorphous state of the drug.
•Enhance super-saturation of
the drug upon dissolution by
preventing nucleation.
Dina Zhang with permission
9
10. Integrate Amorphous Solid Dispersion in the Drug
Discovery Process
Challenges:
• Aggressive timeline requires fast turn-around
– Rely on high throughput screening and platform approaches
• API supply limitations at various stages of Discovery space
– Scaled down process for batch preparation, characterization and
analysis
• Cross-functional collaboration is required
– High throughput screening
– Formulation preparation
– Characterization and analysis
– Troubleshooting
– Scale up
10
11. Screening For Solvents and Polymers
• Solvent Selection is based on solubility (> 10 mg/mL) and compatibility
• Acetone, MeOH, EtOH, IPA, t-BuOH, EtOAc, IPOAc, Toluene, HOAc,
MEK, THF, DCM plus mixing with H2O (up to 25%)
• Polymer Selection
• Solvent casting screening in 96-well plate
• Polymers: HPMCAS (LF, MF, HF), HPMCP (HP-55), PVP-PVAc(Kollidone
VA64) PVP (Kollidone 90F), Eugragit (L100) and etc.
• Surfactants (optional) to further enhance solubility
• A small amount of film is formed and characterized by microscopy and
PXRD
• Kinetic solubility of dispersed film in FaSSIF
Shanbhag, A. et. al.,International Journal of Pharmaceutics, 351, 209-218 (2008)
Moser, J. D. et. al.. American Pharmaceutical Review, Sep/Oct, 2008
11
12. Scaled Down Process
•ProCepT Microspray Drying
system provides capabilities of Feed Solution
small batch size to Drying
Gas
accommodate limitation of Inlet
+
compound availability in Heater
Discovery space:
Drying
Batch size: 0.25 – 4000 mL Chamber
Particle size range: 2- 75 microns
Processing yield: ~85% for 25 mg of
product
Cyclone
+ Collection Connecting
Vessel Tube
Information provided by ProCepT
12
13. Characterization of Spray-Dried Amorphous Solid
Dispersion
• Physical characterization: mDSC, PXRD and TGA
• Chemical characterization: assay and impurity
profile
• Solid state stability
• In-use stability in suspending vehicle
• Redisperse study in SGF and FaSSIF
• Maximum feasible concentration determination
• Confirm exposure enhancement by
pharmacokinetic studies
13
14. Platform Vehicle and Vehicle Selection
• Platform vehicle:
Suspending agent + Acidifying agent + Wetting agent
• Key Considerations:
– Visual wetting, stirability/suspendability/syringability, at low and high
dose (MFC)
– Physically and chemically stable for at least 4 hours
– Well-dispersed and uniform suspension
– Maximum feasible concentration
– Acidifying agent prevents API released from the pH sensitive polymer to
ensure in-use physical stability
– Low amount of surfactant is added as a wetting agent but may promote
solubilization/dissolution of the API and hence may promote
crystallization.
14
15. Limitations of Spray Dried Amorphous Solid
Dispersion Formulation
• Solubility and compatibility in organic solvents
• Drug loading limitations (Maximum Feasible Concentration
concerns)
• Complexity of workflow in fast-paced Discovery space
• Additional work of scaling up for GLP toxicology studies
15
16. Case Study #1: Using Spray Dried Amorphous Solid
Dispersion Of Compound A For Discovery Toxicology Studies
Rodent PK
16.00
Challenge: Identify a formulation PEG/Tw een (200 mpk)
20% TPGS (200 mpk)
strategy to provide exposure Nanoformulation (100 mpk)
Spray Dried Amorphous (100 mpk)
despite the poor solubility 12.00
(<0.001 mg/mL in SGF and
FaSSIF). 8.00
Spray dried
amorphous solid
AUC
dispersion
In rodents the spray dried formulation
amorphous solid dispersion 4.00
formulation significantly improve
exposure relative to alternative 0.00
formulation strategies. 0 4 8 12 16 20 24
Time (hr)
J. Ormes, J. Chang, D. Leung, E. Kwong, F. Li
16
17. Case Study #2: Using Solid Dispersion Formulation to
Enhance Oral Exposure and Resolve Polymorphism Issues
• Challenges:
1. The compound exhibited polymorphism with numerous crystalline
phases (>20) identified and physical phase instability in the
conventional formulation
2. The compound exhibited a >30x decrease in solubility from
amorphous phase upon identification of a high melting crystalline
form (decline from > 0.600 ug/mL to 0.017 ug/mL).
3. Discovery toxicology formulation had to be developed within two
weeks to meet program timeline
M. Hu, J. Ormes, J. Chang, E. Kwong, A. Bak, C. Alleyne, S. Lohani
17
18. Case Study #2: Using Solid Dispersion Formulation to
Enhance Oral Exposure and Resolve Polymorphism Issues
• Spray Dried formulation provided a physically stable
formulation which overcame solubility concerns to provide
sufficient exposure for discovery toxicology studies without
timeline delay.
Cmax AUC(0-x) Exposure Physical Stability
PK 100 mpk in Rat Tmax (h)
(μM) (μMh) Multiple (in vehicle)
Conventional
Formulation
48 2 611 127x unstable
(partially
solubilization)
Nanosuspension
21.5 2 254 53x unstable
(wet milling)
Amorphous Solid
Dispersion 43.8 2.3 686 143x stable
(spray drying)
18
19. Summary
• Spray dried amorphous solid dispersion is a powerful tool for enhancing
bioavailability and providing stable amorphous platform formulations in
Discovery:
– Spray Drying enables compounds with poor solubility to achieve
sufficient oral exposures
– Spray dried amorphous solid dispersion also simplifies formulation
strategy for compounds displaying complex polymorphism.
• By utilizing solvent casting screening, scaled down process and platform
approach, spray-dried amorphous solid dispersion becomes a feasible
formulation strategy in Discovery when API is limited and timeline is
short.
19
20. Acknowledgement
Dennis Leung Justin Moser
Fangbiao Li Mike Lowinger
Candice Alleyne Caroline McGregor
Sachin Lohani Dina Zhang
Vincent Tong Elise Miller
Lina Liu Davida Krueger
Timothy Rhodes Elizabeth Kwong
Patrick Marsac Allen Templeton
Annette Bak Michael Kress
20