preformulation

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methods for preformulation studies

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Preformulation- a new approach: 

Preformulation- a new approach Presented by Dr. vijayan Jagans college of pharmacy Nellore, AP, India.

Preformulation-a new approach: 

Preformulation-a new approach Prior to the development of a formulation (dosage form) with a new drug moiety.

PowerPoint Presentation: 

Important physical and chemical propreties of the drug molecules and other derived property of the drug. Evolved in the years of 1950-1960s Process of optimizing the delivery of drug Determine physiochemical property, efficicacy, stable and safe of new drug.

Objectives : 

Objectives Identity and physiochemical propreties of new drug Kinetic rate profile Compatibility with exicipients

Preformulation testing: 

Preformulation testing Useful to proposal of different dosage forms Selection of route of adm . Solubility useful for choice of formulation and choice of analytical method development. Water content- crystal property, particle size and stabity Particle size- bioavailability, uniformity, solubility, stability Crystal property & polymorphism- solubility, bioavailability/ stability.

Preformulation steps: 

Preformulation steps Identity of drug - UV, IR, MS - physical appearances 2. Development of analytical method -assay method by initially UV -TLC, HPTLC methods. 3. Physiochemical properties a. solubility b. melting point c. physical form d. microscopy characters e. powder flow property.

Organoletic properties: 

Organoletic properties color odor taste Off-white Pungent Acidic Cream yellow Sulfurous Bitter Tan Fruity Bland shiny Aromatic Intense odorless Sweet tasteless

solubility: 

solubility The solubility of drug is an important physicochemical property because it effects the bioavailability of the drug, the rate of drug resale into dissolution medium and consequently, the therapeutic efficiency of the pharmaceutical product. Common solvents used for solubility determination are ·Wate ·Polyethylene Glycols ·Propylene Glycol ·Glycerin ·Sorbitol ·Ethyl Alcohol ·Methanol ·Benzyl Alcohol ·Isopropyl Alcohol ·Tweens ·Polysorbates ·Castor Oil ·Peanut Oil ·Sesame Oil ·Buffer at various pHs

pKa Determination : 

pKa Determination Dissociation content of drug molecules in ionizable solvent of pH 1-10. Choice for absorption rate Henderson – Hasseslebach  equation-estimate of the ionized and un ionized durg concentration at a particular pH. pH = pKa + log  (un-ionized drug]) / [ionized drug])

Partition Coefficient : 

Partition Coefficient measure of a drug’s lipophilicity and ability to cross cell membranes. P o/w = (C oil / C water) P value greater than 1 –lipophilic drug, P value less than 1-hydrophilic drug

Bulk characters: 

Bulk characters Necessary to avoid misleading prediction of stability/ solubility Parameters -crystallinity and polymorphism -characterization of solid forms:

Crystallinity : 

Crystallinity Crystal habit and internal structure of drug can affect bulk & physiochemical characters. Habit: outer appreance of crystal examples; plarity, massive, needle, blade tabular, primatic Internal structure; molecular arrangement within solid. Examples: crystals, amorphous form.m

Cont....: 

Cont.... Crystal shape; repetitious spacing of constituents atom/ molecules in 3D array Amorphous shape: atoms, molecules randomly placed in liquid. Solubility& dissolution rate is more in amorphous than crystal.

polymorphism: 

polymorphism

Methods of characterization of solid form: 

Methods of characterization of solid form Microscopy characters -lattices form - polarization characters -refractive index 2. Thermal analysis - DSC & TGA -physical/ chemical changes with in a drug by function of temperature. - purity, polymorphism, salvation, degradation, exicipents compatibility. - X-rays method crystal lattice in a powder.

Fine particles charaterization: 

Fine particles charaterization Various density -bulk - tap - granular - compressible index - hausners ratio

Cont….: 

Cont…. Chemical reactiviy size, shape, surface morphologyty directly affected Particles size - microscopy - sieve method - coulter counter method. Surface area: - air permeability method-BED ( brunauer emmett teller) Surface morphology; - SEM & TEM

Surface area: 

Surface area Diameter um Surface area 0.25 24 0.50 12 1 6 2 3 4 1.5 10 0.63 15 0.4 20 0.3 40 0.15

Power Flow Properties : 

Power Flow Properties Bulk density Tapdensity Granular density Hausners ratio Compressibile index Flow Angle of repose Carr’s index ( % ) Excellent <25 5-15 Good25- 30 12-16 Fair to passable 30-40 18-21 Poor > 40 23-35 Very Poor - 33-38 Extremely Poor -  >40 Changes in particles size, and shape are generally very important an increase in crystal size or a more uniform shape will lead to a small angle or repose  and a smaller Carr’s index.

Chemical stability : 

Chemical stability quantitative  assessment of chemical stability of a new drug Types; Solid state stability - Solution phase stability - Compatibility studies stability in the Presence of exicipients - Typical stability protocol for a new drug.

Solid state stability : 

Solid state stability Chemical instability -hydrolysis, oxidation, photolysis and pyrolysis. The elevated temperatures 40, 50, and 60 C with ambient humidity observed physical and  chemical changes no changes is seen after 30 days at 60 degree centigrade, the stability prognosis is excellent

Solution phase stability : 

Solution phase stability As compared with the dry form, the degradation is much rapid in solution form The pH based stability study, using different stimulator GI condition can be designed . A poor solution stability of drug may urge the formulator to choose a less soluble salt form, provided the bioavailability is not compromised

Compatibility studies : 

Compatibility studies drug exicipients interaction is useful for the formulation to select appropriate exicipients Methods: DSC TGA X-rays

Conclusion : 

Conclusion Preformulation studies have a significant part to play in anticipating formulation problems and identifying logical path for all dosage forms.

PowerPoint Presentation: 

Test Method/ function Characterization Fundamental 1) UV spectroscopy Simple assay 2) Solubility Phase solubility/ purity a) Aqueous Intrinsic & pH effect b) pKa solubility control , salt formation c) Salt Solubility, hygroscopicity & stability d)Solvents Vehicles & Extraction e) ko/ w Lipophillicity, structure activity f) Dissolution Biopharmacy 3) Melting point DSC-polymorphism hydrate & solvent 4) Assay development UV, HPLC, TLC 5) Stability In Solution Thermal, hydrolysis, pH In solid state Oxidation, proteolysis metal ion Derived 6) Microscopy Particle size and morphology 7) Bulk density Tablet and capsule formation 8) Flow properties Tablet and capsule formation 9) Compression properties Acid / excipient choice 10) Excipient compatibility Preliminary screen by DSC, Conformation by TLC