[{"data":1,"prerenderedAt":1699},["ShallowReactive",2],{"mdc--p0h6tp-key":3},{"data":4,"body":5},{},{"type":6,"children":7},"root",[8,17,31,43,48,88,92,98,105,155,161,166,194,206,212,217,284,302,305,311,317,322,340,352,355,361,366,399,402,408,441,444,450,455,488,507,525,528,534,581,584,590,628,631,637,643,673,676,682,733,757,760,766,778,796,808,811,817,823,846,849,855,883,900,903,909,932,937,950,953,959,1002,1016,1019,1025,1031,1036,1039,1045,1068,1071,1077,1100,1103,1109,1149,1165,1168,1174,1179,1223,1226,1232,1255,1258,1264,1297,1314,1317,1323,1329,1347,1350,1356,1378,1381,1387,1410,1421,1424,1430,1436,1454,1457,1463,1486,1489,1494,1512,1515,1521,1539,1542,1548,1554,1580,1583,1589,1602,1605,1611,1629,1632,1638,1644,1682,1688],{"type":9,"tag":10,"props":11,"children":13},"element","h2",{"id":12},"paper-overview-purpose",[14],{"type":15,"value":16},"text","📘 Paper overview & purpose",{"type":9,"tag":18,"props":19,"children":20},"p",{},[21,23,29],{"type":15,"value":22},"This review explains ",{"type":9,"tag":24,"props":25,"children":26},"strong",{},[27],{"type":15,"value":28},"how amino acids (AAs) are used as pharmaceutical excipients and co-formers",{"type":15,"value":30}," to improve drug performance. The central idea is:",{"type":9,"tag":32,"props":33,"children":34},"blockquote",{},[35],{"type":9,"tag":18,"props":36,"children":37},{},[38],{"type":9,"tag":24,"props":39,"children":40},{},[41],{"type":15,"value":42},"Amino acids can improve solubility, stability, permeability, bioavailability, and therapeutic efficacy of drugs—often without changing the drug’s pharmacology.",{"type":9,"tag":18,"props":44,"children":45},{},[46],{"type":15,"value":47},"The paper covers:",{"type":9,"tag":49,"props":50,"children":51},"ul",{},[52,58,63,68,73,78,83],{"type":9,"tag":53,"props":54,"children":55},"li",{},[56],{"type":15,"value":57},"AA structure & classification",{"type":9,"tag":53,"props":59,"children":60},{},[61],{"type":15,"value":62},"Safety and regulation",{"type":9,"tag":53,"props":64,"children":65},{},[66],{"type":15,"value":67},"Manufacturing techniques",{"type":9,"tag":53,"props":69,"children":70},{},[71],{"type":15,"value":72},"Effects on solubility, stability, permeability",{"type":9,"tag":53,"props":74,"children":75},{},[76],{"type":15,"value":77},"Multicomponent systems",{"type":9,"tag":53,"props":79,"children":80},{},[81],{"type":15,"value":82},"Therapeutic performance",{"type":9,"tag":53,"props":84,"children":85},{},[86],{"type":15,"value":87},"Future outlook",{"type":9,"tag":89,"props":90,"children":91},"hr",{},[],{"type":9,"tag":10,"props":93,"children":95},{"id":94},"_1️⃣-introduction-why-amino-acids-matter-in-pharmaceutics",[96],{"type":15,"value":97},"1️⃣ Introduction: Why amino acids matter in pharmaceutics 💊",{"type":9,"tag":99,"props":100,"children":102},"h3",{"id":101},"the-core-problem",[103],{"type":15,"value":104},"The core problem",{"type":9,"tag":49,"props":106,"children":107},{},[108,143],{"type":9,"tag":53,"props":109,"children":110},{},[111,113,118,120],{"type":15,"value":112},"~",{"type":9,"tag":24,"props":114,"children":115},{},[116],{"type":15,"value":117},"40% of drug molecules",{"type":15,"value":119}," have poor physicochemical properties:",{"type":9,"tag":49,"props":121,"children":122},{},[123,128,133,138],{"type":9,"tag":53,"props":124,"children":125},{},[126],{"type":15,"value":127},"Low solubility",{"type":9,"tag":53,"props":129,"children":130},{},[131],{"type":15,"value":132},"Poor permeability",{"type":9,"tag":53,"props":134,"children":135},{},[136],{"type":15,"value":137},"Instability",{"type":9,"tag":53,"props":139,"children":140},{},[141],{"type":15,"value":142},"Unfavorable pKa or lipophilicity",{"type":9,"tag":53,"props":144,"children":145},{},[146,148,153],{"type":15,"value":147},"These issues limit ",{"type":9,"tag":24,"props":149,"children":150},{},[151],{"type":15,"value":152},"oral bioavailability",{"type":15,"value":154}," and formulation success.",{"type":9,"tag":99,"props":156,"children":158},{"id":157},"traditional-solutions",[159],{"type":15,"value":160},"Traditional solutions",{"type":9,"tag":18,"props":162,"children":163},{},[164],{"type":15,"value":165},"Techniques like:",{"type":9,"tag":49,"props":167,"children":168},{},[169,174,179,184,189],{"type":9,"tag":53,"props":170,"children":171},{},[172],{"type":15,"value":173},"Salt formation",{"type":9,"tag":53,"props":175,"children":176},{},[177],{"type":15,"value":178},"Solid dispersions",{"type":9,"tag":53,"props":180,"children":181},{},[182],{"type":15,"value":183},"Cyclodextrin complexation",{"type":9,"tag":53,"props":185,"children":186},{},[187],{"type":15,"value":188},"Nanocrystals",{"type":9,"tag":53,"props":190,"children":191},{},[192],{"type":15,"value":193},"Lipid systems",{"type":9,"tag":18,"props":195,"children":196},{},[197,199,204],{"type":15,"value":198},"➡️ Often effective, but ",{"type":9,"tag":24,"props":200,"children":201},{},[202],{"type":15,"value":203},"complex, costly, or poorly scalable",{"type":15,"value":205},".",{"type":9,"tag":99,"props":207,"children":209},{"id":208},"why-amino-acids",[210],{"type":15,"value":211},"Why amino acids?",{"type":9,"tag":18,"props":213,"children":214},{},[215],{"type":15,"value":216},"Amino acids are attractive because they:",{"type":9,"tag":49,"props":218,"children":219},{},[220,230,240,250,260],{"type":9,"tag":53,"props":221,"children":222},{},[223,225],{"type":15,"value":224},"Are ",{"type":9,"tag":24,"props":226,"children":227},{},[228],{"type":15,"value":229},"small, natural, biodegradable molecules",{"type":9,"tag":53,"props":231,"children":232},{},[233,235],{"type":15,"value":234},"Possess ",{"type":9,"tag":24,"props":236,"children":237},{},[238],{"type":15,"value":239},"amino + carboxyl groups",{"type":9,"tag":53,"props":241,"children":242},{},[243,245],{"type":15,"value":244},"Can form ",{"type":9,"tag":24,"props":246,"children":247},{},[248],{"type":15,"value":249},"hydrogen bonds, ionic, and hydrophobic interactions",{"type":9,"tag":53,"props":251,"children":252},{},[253,255],{"type":15,"value":254},"Are often ",{"type":9,"tag":24,"props":256,"children":257},{},[258],{"type":15,"value":259},"GRAS / biocompatible",{"type":9,"tag":53,"props":261,"children":262},{},[263,265,270,272,277,279],{"type":15,"value":264},"Can act as ",{"type":9,"tag":24,"props":266,"children":267},{},[268],{"type":15,"value":269},"co-formers",{"type":15,"value":271},", ",{"type":9,"tag":24,"props":273,"children":274},{},[275],{"type":15,"value":276},"stabilizers",{"type":15,"value":278},", or ",{"type":9,"tag":24,"props":280,"children":281},{},[282],{"type":15,"value":283},"permeation enhancers",{"type":9,"tag":18,"props":285,"children":286},{},[287,289,294,296,301],{"type":15,"value":288},"🧠 ",{"type":9,"tag":24,"props":290,"children":291},{},[292],{"type":15,"value":293},"Key idea:",{"type":15,"value":295}," Amino acids are not just nutrients—they are ",{"type":9,"tag":24,"props":297,"children":298},{},[299],{"type":15,"value":300},"functional pharmaceutical tools",{"type":15,"value":205},{"type":9,"tag":89,"props":303,"children":304},{},[],{"type":9,"tag":10,"props":306,"children":308},{"id":307},"_2️⃣-amino-acid-structure-properties",[309],{"type":15,"value":310},"2️⃣ Amino acid structure & properties 🧬",{"type":9,"tag":99,"props":312,"children":314},{"id":313},"general-structure",[315],{"type":15,"value":316},"General structure",{"type":9,"tag":18,"props":318,"children":319},{},[320],{"type":15,"value":321},"All amino acids contain:",{"type":9,"tag":49,"props":323,"children":324},{},[325,330,335],{"type":9,"tag":53,"props":326,"children":327},{},[328],{"type":15,"value":329},"α-amino group (–NH₂ / –NH₃⁺)",{"type":9,"tag":53,"props":331,"children":332},{},[333],{"type":15,"value":334},"α-carboxyl group (–COOH / –COO⁻)",{"type":9,"tag":53,"props":336,"children":337},{},[338],{"type":15,"value":339},"Side chain (R-group) → determines behavior",{"type":9,"tag":18,"props":341,"children":342},{},[343,345,350],{"type":15,"value":344},"They exist as ",{"type":9,"tag":24,"props":346,"children":347},{},[348],{"type":15,"value":349},"zwitterions",{"type":15,"value":351}," at physiological pH.",{"type":9,"tag":89,"props":353,"children":354},{},[],{"type":9,"tag":99,"props":356,"children":358},{"id":357},"functional-roles-in-biology",[359],{"type":15,"value":360},"Functional roles in biology",{"type":9,"tag":18,"props":362,"children":363},{},[364],{"type":15,"value":365},"AAs are involved in:",{"type":9,"tag":49,"props":367,"children":368},{},[369,374,379,384,389,394],{"type":9,"tag":53,"props":370,"children":371},{},[372],{"type":15,"value":373},"Protein synthesis",{"type":9,"tag":53,"props":375,"children":376},{},[377],{"type":15,"value":378},"Metabolism",{"type":9,"tag":53,"props":380,"children":381},{},[382],{"type":15,"value":383},"Osmoregulation",{"type":9,"tag":53,"props":385,"children":386},{},[387],{"type":15,"value":388},"Hormone secretion",{"type":9,"tag":53,"props":390,"children":391},{},[392],{"type":15,"value":393},"Cell signaling",{"type":9,"tag":53,"props":395,"children":396},{},[397],{"type":15,"value":398},"Gene regulation",{"type":9,"tag":89,"props":400,"children":401},{},[],{"type":9,"tag":99,"props":403,"children":405},{"id":404},"nutritional-classification",[406],{"type":15,"value":407},"Nutritional classification",{"type":9,"tag":49,"props":409,"children":410},{},[411,421,431],{"type":9,"tag":53,"props":412,"children":413},{},[414,419],{"type":9,"tag":24,"props":415,"children":416},{},[417],{"type":15,"value":418},"Essential AAs",{"type":15,"value":420}," (must come from diet):\nHIS, ILE, LEU, LYS, MET, PHE, THR, TRP, VAL",{"type":9,"tag":53,"props":422,"children":423},{},[424,429],{"type":9,"tag":24,"props":425,"children":426},{},[427],{"type":15,"value":428},"Non-essential AAs",{"type":15,"value":430},": synthesized by body",{"type":9,"tag":53,"props":432,"children":433},{},[434,439],{"type":9,"tag":24,"props":435,"children":436},{},[437],{"type":15,"value":438},"Conditionally essential AAs",{"type":15,"value":440},": required during stress/illness (e.g., ARG, GLN)",{"type":9,"tag":89,"props":442,"children":443},{},[],{"type":9,"tag":99,"props":445,"children":447},{"id":446},"chemical-physicochemical-classification",[448],{"type":15,"value":449},"Chemical & physicochemical classification",{"type":9,"tag":18,"props":451,"children":452},{},[453],{"type":15,"value":454},"AAs are grouped by:",{"type":9,"tag":49,"props":456,"children":457},{},[458,463,468,473,478,483],{"type":9,"tag":53,"props":459,"children":460},{},[461],{"type":15,"value":462},"Acidic (ASP, GLU)",{"type":9,"tag":53,"props":464,"children":465},{},[466],{"type":15,"value":467},"Basic (ARG, LYS, HIS)",{"type":9,"tag":53,"props":469,"children":470},{},[471],{"type":15,"value":472},"Aromatic (PHE, TYR, TRP)",{"type":9,"tag":53,"props":474,"children":475},{},[476],{"type":15,"value":477},"Sulfur-containing (CYS, MET)",{"type":9,"tag":53,"props":479,"children":480},{},[481],{"type":15,"value":482},"Hydrophobic vs hydrophilic",{"type":9,"tag":53,"props":484,"children":485},{},[486],{"type":15,"value":487},"Ionisable vs non-ionisable",{"type":9,"tag":18,"props":489,"children":490},{},[491,493,498,500,505],{"type":15,"value":492},"📌 ",{"type":9,"tag":24,"props":494,"children":495},{},[496],{"type":15,"value":497},"Why this matters pharmaceutically:",{"type":15,"value":499},"\nAA ",{"type":9,"tag":24,"props":501,"children":502},{},[503],{"type":15,"value":504},"charge, solubility, and side-chain chemistry",{"type":15,"value":506}," determine:",{"type":9,"tag":49,"props":508,"children":509},{},[510,515,520],{"type":9,"tag":53,"props":511,"children":512},{},[513],{"type":15,"value":514},"Drug–AA compatibility",{"type":9,"tag":53,"props":516,"children":517},{},[518],{"type":15,"value":519},"Type of interaction (salt, cocrystal, co-amorphous)",{"type":9,"tag":53,"props":521,"children":522},{},[523],{"type":15,"value":524},"Final formulation behavior",{"type":9,"tag":89,"props":526,"children":527},{},[],{"type":9,"tag":99,"props":529,"children":531},{"id":530},"pka-pi-and-ionization",[532],{"type":15,"value":533},"pKa, pI, and ionization",{"type":9,"tag":49,"props":535,"children":536},{},[537,547,559],{"type":9,"tag":53,"props":538,"children":539},{},[540,542],{"type":15,"value":541},"AAs have ",{"type":9,"tag":24,"props":543,"children":544},{},[545],{"type":15,"value":546},"multiple pKa values",{"type":9,"tag":53,"props":548,"children":549},{},[550,552,557],{"type":15,"value":551},"At ",{"type":9,"tag":24,"props":553,"children":554},{},[555],{"type":15,"value":556},"isoelectric point (pI)",{"type":15,"value":558}," → net charge = 0",{"type":9,"tag":53,"props":560,"children":561},{},[562,564],{"type":15,"value":563},"Ionization state affects:",{"type":9,"tag":49,"props":565,"children":566},{},[567,572,576],{"type":9,"tag":53,"props":568,"children":569},{},[570],{"type":15,"value":571},"Solubility",{"type":9,"tag":53,"props":573,"children":574},{},[575],{"type":15,"value":173},{"type":9,"tag":53,"props":577,"children":578},{},[579],{"type":15,"value":580},"Molecular interactions",{"type":9,"tag":89,"props":582,"children":583},{},[],{"type":9,"tag":99,"props":585,"children":587},{"id":586},"chirality-stability",[588],{"type":15,"value":589},"Chirality & stability",{"type":9,"tag":49,"props":591,"children":592},{},[593,605,610],{"type":9,"tag":53,"props":594,"children":595},{},[596,598,603],{"type":15,"value":597},"All AAs except ",{"type":9,"tag":24,"props":599,"children":600},{},[601],{"type":15,"value":602},"glycine",{"type":15,"value":604}," are chiral (L/D forms)",{"type":9,"tag":53,"props":606,"children":607},{},[608],{"type":15,"value":609},"L-AAs dominate biology and pharmaceutics",{"type":9,"tag":53,"props":611,"children":612},{},[613,615],{"type":15,"value":614},"Some AAs are chemically sensitive:",{"type":9,"tag":49,"props":616,"children":617},{},[618,623],{"type":9,"tag":53,"props":619,"children":620},{},[621],{"type":15,"value":622},"CYS → oxidation",{"type":9,"tag":53,"props":624,"children":625},{},[626],{"type":15,"value":627},"GLN → cyclization",{"type":9,"tag":89,"props":629,"children":630},{},[],{"type":9,"tag":10,"props":632,"children":634},{"id":633},"_3️⃣-safety-considerations-️",[635],{"type":15,"value":636},"3️⃣ Safety considerations ⚠️",{"type":9,"tag":99,"props":638,"children":640},{"id":639},"general-safety",[641],{"type":15,"value":642},"General safety",{"type":9,"tag":49,"props":644,"children":645},{},[646,656,668],{"type":9,"tag":53,"props":647,"children":648},{},[649,651],{"type":15,"value":650},"AAs are ",{"type":9,"tag":24,"props":652,"children":653},{},[654],{"type":15,"value":655},"endogenous and naturally metabolized",{"type":9,"tag":53,"props":657,"children":658},{},[659,661,666],{"type":15,"value":660},"Oral doses ",{"type":9,"tag":24,"props":662,"children":663},{},[664],{"type":15,"value":665},"0.2–2.5%",{"type":15,"value":667}," are generally safe",{"type":9,"tag":53,"props":669,"children":670},{},[671],{"type":15,"value":672},"Excessive intake → adverse effects possible",{"type":9,"tag":89,"props":674,"children":675},{},[],{"type":9,"tag":99,"props":677,"children":679},{"id":678},"gras-status-regulation",[680],{"type":15,"value":681},"GRAS status & regulation",{"type":9,"tag":49,"props":683,"children":684},{},[685,695,700,705],{"type":9,"tag":53,"props":686,"children":687},{},[688,690],{"type":15,"value":689},"1958: AAs classified as ",{"type":9,"tag":24,"props":691,"children":692},{},[693],{"type":15,"value":694},"GRAS",{"type":9,"tag":53,"props":696,"children":697},{},[698],{"type":15,"value":699},"1972–1977: FDA removed blanket GRAS status",{"type":9,"tag":53,"props":701,"children":702},{},[703],{"type":15,"value":704},"1977 L-tryptophan incident → toxicity outbreak → regulatory caution",{"type":9,"tag":53,"props":706,"children":707},{},[708,710,715],{"type":15,"value":709},"Today: ",{"type":9,"tag":24,"props":711,"children":712},{},[713],{"type":15,"value":714},"AA regulation is context-dependent",{"type":9,"tag":49,"props":716,"children":717},{},[718,723,728],{"type":9,"tag":53,"props":719,"children":720},{},[721],{"type":15,"value":722},"Dose",{"type":9,"tag":53,"props":724,"children":725},{},[726],{"type":15,"value":727},"Route",{"type":9,"tag":53,"props":729,"children":730},{},[731],{"type":15,"value":732},"Intended use (food vs drug)",{"type":9,"tag":18,"props":734,"children":735},{},[736,737,742,744,749,751,756],{"type":15,"value":492},{"type":9,"tag":24,"props":738,"children":739},{},[740],{"type":15,"value":741},"Important distinction:",{"type":15,"value":743},"\nAmino acids may be ",{"type":9,"tag":24,"props":745,"children":746},{},[747],{"type":15,"value":748},"GRAS as nutrients",{"type":15,"value":750},", but ",{"type":9,"tag":24,"props":752,"children":753},{},[754],{"type":15,"value":755},"regulated as drugs when used pharmaceutically",{"type":15,"value":205},{"type":9,"tag":89,"props":758,"children":759},{},[],{"type":9,"tag":99,"props":761,"children":763},{"id":762},"aa-as-excipients-in-approved-drugs",[764],{"type":15,"value":765},"AA as excipients in approved drugs",{"type":9,"tag":18,"props":767,"children":768},{},[769,771,776],{"type":15,"value":770},"AAs like ",{"type":9,"tag":24,"props":772,"children":773},{},[774],{"type":15,"value":775},"ARG, GLY, HIS, GLU",{"type":15,"value":777}," are used as:",{"type":9,"tag":49,"props":779,"children":780},{},[781,786,791],{"type":9,"tag":53,"props":782,"children":783},{},[784],{"type":15,"value":785},"Protein stabilizers",{"type":9,"tag":53,"props":787,"children":788},{},[789],{"type":15,"value":790},"Cryoprotectants",{"type":9,"tag":53,"props":792,"children":793},{},[794],{"type":15,"value":795},"Formulation buffers",{"type":9,"tag":18,"props":797,"children":798},{},[799,801,806],{"type":15,"value":800},"Examples include ",{"type":9,"tag":24,"props":802,"children":803},{},[804],{"type":15,"value":805},"Herceptin®, Activase®, Kogenate® FS",{"type":15,"value":807},", etc.",{"type":9,"tag":89,"props":809,"children":810},{},[],{"type":9,"tag":10,"props":812,"children":814},{"id":813},"_4️⃣-manufacturing-techniques",[815],{"type":15,"value":816},"4️⃣ Manufacturing techniques 🏭",{"type":9,"tag":99,"props":818,"children":820},{"id":819},"why-method-selection-matters",[821],{"type":15,"value":822},"Why method selection matters",{"type":9,"tag":49,"props":824,"children":825},{},[826,831,836,841],{"type":9,"tag":53,"props":827,"children":828},{},[829],{"type":15,"value":830},"Drug + AA compatibility",{"type":9,"tag":53,"props":832,"children":833},{},[834],{"type":15,"value":835},"Physical state (crystalline vs amorphous)",{"type":9,"tag":53,"props":837,"children":838},{},[839],{"type":15,"value":840},"Stability",{"type":9,"tag":53,"props":842,"children":843},{},[844],{"type":15,"value":845},"Scalability",{"type":9,"tag":89,"props":847,"children":848},{},[],{"type":9,"tag":99,"props":850,"children":852},{"id":851},"solution-based-methods",[853],{"type":15,"value":854},"Solution-based methods",{"type":9,"tag":49,"props":856,"children":857},{},[858,863,868,873,878],{"type":9,"tag":53,"props":859,"children":860},{},[861],{"type":15,"value":862},"Co-evaporation",{"type":9,"tag":53,"props":864,"children":865},{},[866],{"type":15,"value":867},"Spray-drying",{"type":9,"tag":53,"props":869,"children":870},{},[871],{"type":15,"value":872},"Freeze-drying",{"type":9,"tag":53,"props":874,"children":875},{},[876],{"type":15,"value":877},"Slow solvent evaporation",{"type":9,"tag":53,"props":879,"children":880},{},[881],{"type":15,"value":882},"Co-precipitation",{"type":9,"tag":18,"props":884,"children":885},{},[886,888,893,895],{"type":15,"value":887},"💡 Often used for ",{"type":9,"tag":24,"props":889,"children":890},{},[891],{"type":15,"value":892},"co-amorphous systems",{"type":15,"value":894}," and ",{"type":9,"tag":24,"props":896,"children":897},{},[898],{"type":15,"value":899},"salts",{"type":9,"tag":89,"props":901,"children":902},{},[],{"type":9,"tag":99,"props":904,"children":906},{"id":905},"solid-state-methods",[907],{"type":15,"value":908},"Solid-state methods",{"type":9,"tag":49,"props":910,"children":911},{},[912,917,922,927],{"type":9,"tag":53,"props":913,"children":914},{},[915],{"type":15,"value":916},"Kneading",{"type":9,"tag":53,"props":918,"children":919},{},[920],{"type":15,"value":921},"Grinding (ball-milling, cryomilling)",{"type":9,"tag":53,"props":923,"children":924},{},[925],{"type":15,"value":926},"Liquid-assisted grinding",{"type":9,"tag":53,"props":928,"children":929},{},[930],{"type":15,"value":931},"Quench cooling",{"type":9,"tag":18,"props":933,"children":934},{},[935],{"type":15,"value":936},"💡 Preferred when:",{"type":9,"tag":49,"props":938,"children":939},{},[940,945],{"type":9,"tag":53,"props":941,"children":942},{},[943],{"type":15,"value":944},"Solvents must be avoided",{"type":9,"tag":53,"props":946,"children":947},{},[948],{"type":15,"value":949},"Green chemistry is desired",{"type":9,"tag":89,"props":951,"children":952},{},[],{"type":9,"tag":99,"props":954,"children":956},{"id":955},"types-of-solid-systems-formed",[957],{"type":15,"value":958},"Types of solid systems formed",{"type":9,"tag":49,"props":960,"children":961},{},[962,970,978,986,994],{"type":9,"tag":53,"props":963,"children":964},{},[965],{"type":9,"tag":24,"props":966,"children":967},{},[968],{"type":15,"value":969},"Co-amorphous blends",{"type":9,"tag":53,"props":971,"children":972},{},[973],{"type":9,"tag":24,"props":974,"children":975},{},[976],{"type":15,"value":977},"Cocrystals",{"type":9,"tag":53,"props":979,"children":980},{},[981],{"type":9,"tag":24,"props":982,"children":983},{},[984],{"type":15,"value":985},"Salts",{"type":9,"tag":53,"props":987,"children":988},{},[989],{"type":9,"tag":24,"props":990,"children":991},{},[992],{"type":15,"value":993},"Salt-cocrystals",{"type":9,"tag":53,"props":995,"children":996},{},[997],{"type":9,"tag":24,"props":998,"children":999},{},[1000],{"type":15,"value":1001},"Ternary/multicomponent systems",{"type":9,"tag":18,"props":1003,"children":1004},{},[1005,1006,1011],{"type":15,"value":492},{"type":9,"tag":24,"props":1007,"children":1008},{},[1009],{"type":15,"value":1010},"Take-home:",{"type":9,"tag":24,"props":1012,"children":1013},{},[1014],{"type":15,"value":1015},"Preparation method influences molecular interactions → which determines stability and performance.",{"type":9,"tag":89,"props":1017,"children":1018},{},[],{"type":9,"tag":10,"props":1020,"children":1022},{"id":1021},"_5️⃣-effects-on-solubility-dissolution-bioavailability",[1023],{"type":15,"value":1024},"5️⃣ Effects on solubility, dissolution & bioavailability 💧",{"type":9,"tag":99,"props":1026,"children":1028},{"id":1027},"the-problem",[1029],{"type":15,"value":1030},"The problem",{"type":9,"tag":18,"props":1032,"children":1033},{},[1034],{"type":15,"value":1035},"Poor solubility → poor dissolution → poor absorption",{"type":9,"tag":89,"props":1037,"children":1038},{},[],{"type":9,"tag":99,"props":1040,"children":1042},{"id":1041},"how-amino-acids-help",[1043],{"type":15,"value":1044},"How amino acids help",{"type":9,"tag":49,"props":1046,"children":1047},{},[1048,1053,1058,1063],{"type":9,"tag":53,"props":1049,"children":1050},{},[1051],{"type":15,"value":1052},"Increase wettability",{"type":9,"tag":53,"props":1054,"children":1055},{},[1056],{"type":15,"value":1057},"Modify microenvironmental pH",{"type":9,"tag":53,"props":1059,"children":1060},{},[1061],{"type":15,"value":1062},"Disrupt crystal lattice",{"type":9,"tag":53,"props":1064,"children":1065},{},[1066],{"type":15,"value":1067},"Form soluble salts or amorphous phases",{"type":9,"tag":89,"props":1069,"children":1070},{},[],{"type":9,"tag":99,"props":1072,"children":1074},{"id":1073},"key-examples",[1075],{"type":15,"value":1076},"Key examples",{"type":9,"tag":49,"props":1078,"children":1079},{},[1080,1085,1090,1095],{"type":9,"tag":53,"props":1081,"children":1082},{},[1083],{"type":15,"value":1084},"Indomethacin + ARG / LYS → ↑ solubility & dissolution",{"type":9,"tag":53,"props":1086,"children":1087},{},[1088],{"type":15,"value":1089},"Glibenclamide + ARG → 2× solubility, better bioavailability",{"type":9,"tag":53,"props":1091,"children":1092},{},[1093],{"type":15,"value":1094},"Ibuprofen arginate → improved pharmacokinetics",{"type":9,"tag":53,"props":1096,"children":1097},{},[1098],{"type":15,"value":1099},"Trimethoprim salts with ASP/GLU → ↑ solubility & activity",{"type":9,"tag":89,"props":1101,"children":1102},{},[],{"type":9,"tag":99,"props":1104,"children":1106},{"id":1105},"aa-vs-cyclodextrins",[1107],{"type":15,"value":1108},"AA vs cyclodextrins",{"type":9,"tag":49,"props":1110,"children":1111},{},[1112,1124],{"type":9,"tag":53,"props":1113,"children":1114},{},[1115,1117,1122],{"type":15,"value":1116},"AAs may solubilize ",{"type":9,"tag":24,"props":1118,"children":1119},{},[1120],{"type":15,"value":1121},"less",{"type":15,"value":1123}," than CDs",{"type":9,"tag":53,"props":1125,"children":1126},{},[1127,1129,1134,1136],{"type":15,"value":1128},"But can yield ",{"type":9,"tag":24,"props":1130,"children":1131},{},[1132],{"type":15,"value":1133},"higher oral bioavailability",{"type":15,"value":1135}," due to:",{"type":9,"tag":49,"props":1137,"children":1138},{},[1139,1144],{"type":9,"tag":53,"props":1140,"children":1141},{},[1142],{"type":15,"value":1143},"Permeation enhancement",{"type":9,"tag":53,"props":1145,"children":1146},{},[1147],{"type":15,"value":1148},"Transporter involvement",{"type":9,"tag":18,"props":1150,"children":1151},{},[1152,1153,1158,1163],{"type":15,"value":492},{"type":9,"tag":24,"props":1154,"children":1155},{},[1156],{"type":15,"value":1157},"Critical insight:",{"type":9,"tag":24,"props":1159,"children":1160},{},[1161],{"type":15,"value":1162},"Solubility ≠ bioavailability",{"type":15,"value":1164},". AAs can enhance absorption even when solubility gains are modest.",{"type":9,"tag":89,"props":1166,"children":1167},{},[],{"type":9,"tag":10,"props":1169,"children":1171},{"id":1170},"_6️⃣-effects-on-drug-stability",[1172],{"type":15,"value":1173},"6️⃣ Effects on drug stability 🧊",{"type":9,"tag":99,"props":1175,"children":1177},{"id":1176},"cocrystals",[1178],{"type":15,"value":977},{"type":9,"tag":49,"props":1180,"children":1181},{},[1182,1203,1213],{"type":9,"tag":53,"props":1183,"children":1184},{},[1185,1187],{"type":15,"value":1186},"Improve:",{"type":9,"tag":49,"props":1188,"children":1189},{},[1190,1194,1198],{"type":9,"tag":53,"props":1191,"children":1192},{},[1193],{"type":15,"value":840},{"type":9,"tag":53,"props":1195,"children":1196},{},[1197],{"type":15,"value":571},{"type":9,"tag":53,"props":1199,"children":1200},{},[1201],{"type":15,"value":1202},"Hygroscopicity",{"type":9,"tag":53,"props":1204,"children":1205},{},[1206,1208],{"type":15,"value":1207},"AAs are ideal ",{"type":9,"tag":24,"props":1209,"children":1210},{},[1211],{"type":15,"value":1212},"zwitterionic co-formers",{"type":9,"tag":53,"props":1214,"children":1215},{},[1216,1221],{"type":9,"tag":24,"props":1217,"children":1218},{},[1219],{"type":15,"value":1220},"Proline",{"type":15,"value":1222}," is especially effective due to rigid ring structure",{"type":9,"tag":89,"props":1224,"children":1225},{},[],{"type":9,"tag":99,"props":1227,"children":1229},{"id":1228},"co-amorphous-systems",[1230],{"type":15,"value":1231},"Co-amorphous systems",{"type":9,"tag":49,"props":1233,"children":1234},{},[1235,1240,1245],{"type":9,"tag":53,"props":1236,"children":1237},{},[1238],{"type":15,"value":1239},"Higher energy → higher solubility",{"type":9,"tag":53,"props":1241,"children":1242},{},[1243],{"type":15,"value":1244},"Normally unstable → recrystallization risk",{"type":9,"tag":53,"props":1246,"children":1247},{},[1248,1250],{"type":15,"value":1249},"AA interactions ",{"type":9,"tag":24,"props":1251,"children":1252},{},[1253],{"type":15,"value":1254},"prevent molecular mobility",{"type":9,"tag":89,"props":1256,"children":1257},{},[],{"type":9,"tag":99,"props":1259,"children":1261},{"id":1260},"general-co-former-rules",[1262],{"type":15,"value":1263},"General co-former rules",{"type":9,"tag":49,"props":1265,"children":1266},{},[1267,1277,1287],{"type":9,"tag":53,"props":1268,"children":1269},{},[1270,1275],{"type":9,"tag":24,"props":1271,"children":1272},{},[1273],{"type":15,"value":1274},"Basic AAs (ARG, LYS, HIS)",{"type":15,"value":1276}," → acidic drugs",{"type":9,"tag":53,"props":1278,"children":1279},{},[1280,1285],{"type":9,"tag":24,"props":1281,"children":1282},{},[1283],{"type":15,"value":1284},"Aromatic AAs (TRP, PHE)",{"type":15,"value":1286}," → neutral/basic drugs",{"type":9,"tag":53,"props":1288,"children":1289},{},[1290,1295],{"type":9,"tag":24,"props":1291,"children":1292},{},[1293],{"type":15,"value":1294},"Aliphatic AAs",{"type":15,"value":1296}," → often poor stabilizers",{"type":9,"tag":18,"props":1298,"children":1299},{},[1300,1301,1306,1308,1313],{"type":15,"value":492},{"type":9,"tag":24,"props":1302,"children":1303},{},[1304],{"type":15,"value":1305},"Key message:",{"type":15,"value":1307},"\nAmino acids can extend amorphous stability from ",{"type":9,"tag":24,"props":1309,"children":1310},{},[1311],{"type":15,"value":1312},"days to years",{"type":15,"value":205},{"type":9,"tag":89,"props":1315,"children":1316},{},[],{"type":9,"tag":10,"props":1318,"children":1320},{"id":1319},"_7️⃣-effects-on-permeability",[1321],{"type":15,"value":1322},"7️⃣ Effects on permeability 🚪",{"type":9,"tag":99,"props":1324,"children":1326},{"id":1325},"importance",[1327],{"type":15,"value":1328},"Importance",{"type":9,"tag":49,"props":1330,"children":1331},{},[1332,1342],{"type":9,"tag":53,"props":1333,"children":1334},{},[1335,1337],{"type":15,"value":1336},"Included in ",{"type":9,"tag":24,"props":1338,"children":1339},{},[1340],{"type":15,"value":1341},"BCS classification",{"type":9,"tag":53,"props":1343,"children":1344},{},[1345],{"type":15,"value":1346},"Critical for oral drugs",{"type":9,"tag":89,"props":1348,"children":1349},{},[],{"type":9,"tag":99,"props":1351,"children":1353},{"id":1352},"mechanisms",[1354],{"type":15,"value":1355},"Mechanisms",{"type":9,"tag":49,"props":1357,"children":1358},{},[1359,1364,1368,1373],{"type":9,"tag":53,"props":1360,"children":1361},{},[1362],{"type":15,"value":1363},"Prodrug formation",{"type":9,"tag":53,"props":1365,"children":1366},{},[1367],{"type":15,"value":173},{"type":9,"tag":53,"props":1369,"children":1370},{},[1371],{"type":15,"value":1372},"Ion-pairing",{"type":9,"tag":53,"props":1374,"children":1375},{},[1376],{"type":15,"value":1377},"Transporter targeting (PEPT, LAT1)",{"type":9,"tag":89,"props":1379,"children":1380},{},[],{"type":9,"tag":99,"props":1382,"children":1384},{"id":1383},"examples",[1385],{"type":15,"value":1386},"Examples",{"type":9,"tag":49,"props":1388,"children":1389},{},[1390,1395,1400,1405],{"type":9,"tag":53,"props":1391,"children":1392},{},[1393],{"type":15,"value":1394},"Floxuridine-ILE prodrug → 8× permeability",{"type":9,"tag":53,"props":1396,"children":1397},{},[1398],{"type":15,"value":1399},"Quercetin-AA conjugates → ↑ intestinal transport",{"type":9,"tag":53,"props":1401,"children":1402},{},[1403],{"type":15,"value":1404},"Glibenclamide-ARG → 5× permeation",{"type":9,"tag":53,"props":1406,"children":1407},{},[1408],{"type":15,"value":1409},"Insulin-AA ion pairs → ↑ buccal permeability",{"type":9,"tag":18,"props":1411,"children":1412},{},[1413,1414,1419],{"type":15,"value":492},{"type":9,"tag":24,"props":1415,"children":1416},{},[1417],{"type":15,"value":1418},"Subtle but crucial:",{"type":15,"value":1420},"\nCharge balance and AA concentration determine whether permeability increases or decreases.",{"type":9,"tag":89,"props":1422,"children":1423},{},[],{"type":9,"tag":10,"props":1425,"children":1427},{"id":1426},"_8️⃣-multicomponent-systems",[1428],{"type":15,"value":1429},"8️⃣ Multicomponent systems 🧩",{"type":9,"tag":99,"props":1431,"children":1433},{"id":1432},"what-they-are",[1434],{"type":15,"value":1435},"What they are",{"type":9,"tag":49,"props":1437,"children":1438},{},[1439,1444],{"type":9,"tag":53,"props":1440,"children":1441},{},[1442],{"type":15,"value":1443},"Binary system (drug + host) + AA as third component",{"type":9,"tag":53,"props":1445,"children":1446},{},[1447,1449],{"type":15,"value":1448},"AA acts as ",{"type":9,"tag":24,"props":1450,"children":1451},{},[1452],{"type":15,"value":1453},"auxiliary modulator",{"type":9,"tag":89,"props":1455,"children":1456},{},[],{"type":9,"tag":99,"props":1458,"children":1460},{"id":1459},"benefits",[1461],{"type":15,"value":1462},"Benefits",{"type":9,"tag":49,"props":1464,"children":1465},{},[1466,1471,1476,1481],{"type":9,"tag":53,"props":1467,"children":1468},{},[1469],{"type":15,"value":1470},"Enhanced solubility",{"type":9,"tag":53,"props":1472,"children":1473},{},[1474],{"type":15,"value":1475},"Reduced excipient load",{"type":9,"tag":53,"props":1477,"children":1478},{},[1479],{"type":15,"value":1480},"Improved biological activity",{"type":9,"tag":53,"props":1482,"children":1483},{},[1484],{"type":15,"value":1485},"Reduced toxicity",{"type":9,"tag":89,"props":1487,"children":1488},{},[],{"type":9,"tag":99,"props":1490,"children":1492},{"id":1491},"examples-1",[1493],{"type":15,"value":1386},{"type":9,"tag":49,"props":1495,"children":1496},{},[1497,1502,1507],{"type":9,"tag":53,"props":1498,"children":1499},{},[1500],{"type":15,"value":1501},"Rifampicin + β-CD + ARG → ↑ solubility + antibiofilm effect",{"type":9,"tag":53,"props":1503,"children":1504},{},[1505],{"type":15,"value":1506},"Furosemide + β-CD + ARG → 130× solubility increase",{"type":9,"tag":53,"props":1508,"children":1509},{},[1510],{"type":15,"value":1511},"Albendazole + maltodextrin + GLU → ↑ dissolution (1% → 87%)",{"type":9,"tag":89,"props":1513,"children":1514},{},[],{"type":9,"tag":99,"props":1516,"children":1518},{"id":1517},"aa-functionalized-hydrogels",[1519],{"type":15,"value":1520},"AA-functionalized hydrogels",{"type":9,"tag":49,"props":1522,"children":1523},{},[1524,1529,1534],{"type":9,"tag":53,"props":1525,"children":1526},{},[1527],{"type":15,"value":1528},"Controlled release",{"type":9,"tag":53,"props":1530,"children":1531},{},[1532],{"type":15,"value":1533},"pH- and temperature-responsive",{"type":9,"tag":53,"props":1535,"children":1536},{},[1537],{"type":15,"value":1538},"Applications in ocular & psychiatric therapy",{"type":9,"tag":89,"props":1540,"children":1541},{},[],{"type":9,"tag":10,"props":1543,"children":1545},{"id":1544},"_9️⃣-effects-on-therapeutic-performance",[1546],{"type":15,"value":1547},"9️⃣ Effects on therapeutic performance 🧪",{"type":9,"tag":99,"props":1549,"children":1551},{"id":1550},"improved-pharmacokinetics",[1552],{"type":15,"value":1553},"Improved pharmacokinetics",{"type":9,"tag":49,"props":1555,"children":1556},{},[1557],{"type":9,"tag":53,"props":1558,"children":1559},{},[1560,1562],{"type":15,"value":1561},"Naproxen–L-alanine cocrystal:",{"type":9,"tag":49,"props":1563,"children":1564},{},[1565,1570,1575],{"type":9,"tag":53,"props":1566,"children":1567},{},[1568],{"type":15,"value":1569},"↑ bioavailability",{"type":9,"tag":53,"props":1571,"children":1572},{},[1573],{"type":15,"value":1574},"↓ gastric irritation",{"type":9,"tag":53,"props":1576,"children":1577},{},[1578],{"type":15,"value":1579},"Longer therapeutic action",{"type":9,"tag":89,"props":1581,"children":1582},{},[],{"type":9,"tag":99,"props":1584,"children":1586},{"id":1585},"enhanced-efficacy",[1587],{"type":15,"value":1588},"Enhanced efficacy",{"type":9,"tag":49,"props":1590,"children":1591},{},[1592,1597],{"type":9,"tag":53,"props":1593,"children":1594},{},[1595],{"type":15,"value":1596},"Itraconazole–AA cocrystals → stronger antifungal action",{"type":9,"tag":53,"props":1598,"children":1599},{},[1600],{"type":15,"value":1601},"Indomethacin–PRO cocrystal → faster onset + longer half-life",{"type":9,"tag":89,"props":1603,"children":1604},{},[],{"type":9,"tag":99,"props":1606,"children":1608},{"id":1607},"targeted-delivery",[1609],{"type":15,"value":1610},"Targeted delivery",{"type":9,"tag":49,"props":1612,"children":1613},{},[1614,1624],{"type":9,"tag":53,"props":1615,"children":1616},{},[1617,1619],{"type":15,"value":1618},"AA-drug conjugates exploit ",{"type":9,"tag":24,"props":1620,"children":1621},{},[1622],{"type":15,"value":1623},"AA transporters overexpressed in tumors",{"type":9,"tag":53,"props":1625,"children":1626},{},[1627],{"type":15,"value":1628},"Example: ASP-doxorubicin → ↑ tumor accumulation, ↓ off-target toxicity",{"type":9,"tag":89,"props":1630,"children":1631},{},[],{"type":9,"tag":10,"props":1633,"children":1635},{"id":1634},"conclusions-big-picture",[1636],{"type":15,"value":1637},"🔟 Conclusions & big picture 🎯",{"type":9,"tag":99,"props":1639,"children":1641},{"id":1640},"why-amino-acids-are-powerful-excipients",[1642],{"type":15,"value":1643},"Why amino acids are powerful excipients",{"type":9,"tag":49,"props":1645,"children":1646},{},[1647,1652,1657],{"type":9,"tag":53,"props":1648,"children":1649},{},[1650],{"type":15,"value":1651},"Safe, natural, biodegradable",{"type":9,"tag":53,"props":1653,"children":1654},{},[1655],{"type":15,"value":1656},"Multifunctional (solubility, stability, permeability)",{"type":9,"tag":53,"props":1658,"children":1659},{},[1660,1662],{"type":15,"value":1661},"Enable:",{"type":9,"tag":49,"props":1663,"children":1664},{},[1665,1669,1673,1677],{"type":9,"tag":53,"props":1666,"children":1667},{},[1668],{"type":15,"value":985},{"type":9,"tag":53,"props":1670,"children":1671},{},[1672],{"type":15,"value":977},{"type":9,"tag":53,"props":1674,"children":1675},{},[1676],{"type":15,"value":1231},{"type":9,"tag":53,"props":1678,"children":1679},{},[1680],{"type":15,"value":1681},"Multicomponent platforms",{"type":9,"tag":99,"props":1683,"children":1685},{"id":1684},"final-takeaway",[1686],{"type":15,"value":1687},"Final takeaway",{"type":9,"tag":32,"props":1689,"children":1690},{},[1691],{"type":9,"tag":18,"props":1692,"children":1693},{},[1694],{"type":9,"tag":24,"props":1695,"children":1696},{},[1697],{"type":15,"value":1698},"Amino acids are low-molecular-weight excipients that can transform poorly performing drugs into clinically viable therapies—often with simpler, greener, and safer formulations.",1775084290161]