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Edit Comment Close Premium member Presentation Transcript SOLID-SOLD STABILITY: SOLID-SOLD STABILITY Presented by- AKASH DEEP M.Pharm [ANALYSIS] I.S.F.College of pharmacy,moga [ punjab ]STABILITY: STABILITY Stability of a drug substance or product is defind as the extent to which a product or substance remains within specified limits of identity, strength quality, and purity throughout its period of storage and use.21 CFR 211.166 STABILITY TESTING GMP: 21 CFR 211.166 STABILITY TESTING GMP To assess stability characterstis determining storage condition and expiration date Stressed testing conducted under accelerated or long term storage condition to genrate degraded product of API or product.WHY STABILITY: WHY STABILITY It provides an evidance on how the quality of a drug product degrades with time under the influnce of various factor- Temprature Humidity Light Shelf life of drug product Storage condition solventSOLID STATE STABILITY : SOLID STATE STABILITY The stability of drugs in solid dosage form is most important and common for the study of degradation of drug substance or drug product. Solid dosage form decomposes by either first- or zero-order profile.Solid State Stability: Effect of Excipients: Solid State Stability: Effect of Excipients • Acting as surface catalysts • Acting as a source for extra moisture − Physical state and mobility of water molecules • Altering the pH of the moisture layer • Undergoing direct chemical reactions with the drug − Drug:excipient ratio − Powder mixing and packing • Physical mixing vs. granulation • Granules vs. compactsSolid State Stability: Other Factors: Solid State Stability: Other Factors • Particles − Physical form − Particle size/surface area − Morphology − Defects concentration − ImpuritiesSolid State Stability: Other Factors: Solid State Stability: Other Factors • Environment − Temperature − Relative humidity − Packaging − Light − Oxygen − Moisture • Microbial contamination • Trace metal Contamination • Leaching from containersSolid State Stability: Physical: Solid State Stability: Physical • Physical Changes − Polymorphic transition − Amorphous form − Hydrate formation − Crystallization materialPOLYMORPHISM: POLYMORPHISM Polymorphism is solid phase of given compound with at least two molecular arrengement in crystal lattice or solid structure. According to FDA,drug substance exists in multiple solid-state form,whether these affect bioavailability and dissolution of drug product.TECHNIQUES OF DETERMINING POLYMORPHS: TECHNIQUES OF DETERMINING POLYMORPHS Analytical techniques- −X-Ray powder diffrection [XRPD] −Differential Scanning Calorimetry [DSC] These analytical techniques have been use for quantitative and qualitative analysis of polymorphs.Slide 12: In 1998,Abbott Laboratories had to halt sales of its HIV protease inhibitor ( ritonavir ) in solution-filled softgel capsules, because a more stable , previously unknown polymorph (Form II) suddenly appeared, causing slowed dissolution and compromising the oral bioavailability of the marketed dosage form.HYDRATES: HYDRATES Hydrate is a special class of solvate form where the solvent molecule in the crystal structure is water. In higher relative humidity[RH] drug substance can form hydrateTECHNIQUES OF DETERMINING HYDRATES : TECHNIQUES OF DETERMINING HYDRATES Humidity-controlled thermogravimetric analysis (TGA), − XRPD − Diffuse reflectance infrared Fourier-transform spectroscopy (DRIFTS) − Near-infrared (NIR) Spectroscopy −Terahertz Pulsed SpectroscopyDEHYDRATION PROCESS OF HYDRATE FORM: DEHYDRATION PROCESS OF HYDRATE FORM Step 1. Activation of bound water over energy barrier to become mobile water in the crystal lattice Step 2. Water molecule diffuses to the crystal surface Step 3. Convective mass-transfer of water molecules into the atmosphere or carrier gas Step 4. Formation of the dehydrated crystalline form or collapse of crystal lattice to the amorphous formAMORPHOUS FORM: AMORPHOUS FORM The amorphous form,is thermodynamically metastable solid state which lacks long-range order at the molecular level. Amorphous phase can be formed in many ways either intentionally or unintentionally during the manufacturing processes.Slide 17: Intentional Unintentional • Lyophilization • Spray drying • Melt extrusion • Melt quench cooling • Solution evaporation • Solid dispersion/solution • Co-grinding with inorganic carriers • Wet granulation • Milling/grinding ( micronization ) • Compaction/compression • Desolvation /dehydration • Anti-solvent precipitation • Irradiation • Supercritical fluid processANALYTICAL TECHNIQUES FOR STABILITY STUDIES OF AMORPHOUS: ANALYTICAL TECHNIQUES FOR STABILITY STUDIES OF AMORPHOUS Molecular level/spectroscopy Surface/local FT-IR, ATR, DRIFT FT-Raman Solid-state NMR Near infrared spectroscopy (NIR) Terahertz pulsed spectroscopy Polarized light microscopy (PLM) Scan electron microscopy (SEM) Microscopic image analysis Atomic force microscopy (AFM) Inverse gas chromatography (IGC)CRYSTALINE MATERIAL: CRYSTALINE MATERIAL Physical changes of crystalline drug substances may include four steps- 1 Loosening of intermolecular interactions Non-covalent bonds, [hydrogen bonding, van der Waals force] effect of environmental factors (e.g., heat, light,mechanic forces, solvent, and moisture) defects on crystal surface 2 Rearrangement of molecule orientations or intermolecular confirmations loss of solvent/water molecules from solvate/hydrate forms depending on storage condition Amorphous phase may be formed as the intermediate phase environmental factors (e.g., temperature, oxygen and moisture) 3 Nucleation of new phase Homogeneous or heterogeneous 4 Crystal growth and formation of new formREFRENCE: REFRENCE Huynh– ba , K, (2009), Hand Book of stability testing in pharmaceutical department ; Cartenson , J.T,(1995), Drug stability; principle and practices, Marcel Dekker, Inc.New York. Yoshioka sumie , stella J, stability of drug and dosage form . www.pharmapedia.com.THANK YOU: THANK YOU You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.