©上特 “-wl 国生 Advantages of hard capsules Capsules ·Conceal the smell Improve drug stability Bioavailability is generally good School of Pharmacy Chen Jian Flexibility in formulation 2013.4 chenjian@sjtu.edu.cn Obtain sustained-release Widely used in preliminary drug study 图生一 国生 Capsules are solid dosage forms in which the Disadvantages of hard capsules drug substance is enclosed within either a hard .Filling equipment slower than tableting or soft soluble shell. Extra expense on shells Unsuitable for some kinds of drugs ·Hard capsules Highly soluble materials ·Soft capsules Water or alcohol solution of drugs Efflorescent materials .Hygroscopic materials 国垫生一 圈生一 ©Gelatin capsules Manufacture of hard Capsules Generally the shells of capsules are Gelatin is the most popular component to prepare capsule shells formed from gelatin. Gelatin is prepared by the hydrolysis of ©Nongelatin capsules collagen obtained from animal connective ·HPMC tissue,bones,skin,and sinew. ·Staruch ·Type A ·Type B 1
1 Capsules School of Pharmacy Chen Jian 2013.4 chenjian@sjtu.edu.cn Shanghai Jiao Tong University Capsules are solid dosage forms in which the drug substance is enclosed within either a hard or soft soluble shell. • Hard capsules • Soft capsules Shanghai Jiao Tong University Gelatin capsules • Generally the shells of capsules are formed from gelatin. Nongelatin capsules • HPMC • Staruch Shanghai Jiao Tong University Advantages of hard capsules • Conceal the smell • Improve drug stability • Bioavailability is generally good • Flexibility in formulation • Obtain sustained-release • Widely used in preliminary drug study Shanghai Jiao Tong University Disadvantages of hard capsules • Filling equipment slower than tableting • Extra expense on shells • Unsuitable for some kinds of drugs • Highly soluble materials • Water or alcohol solution of drugs • Efflorescent materials • Hygroscopic materials Shanghai Jiao Tong University Manufacture of hard Capsules • Gelatin is the most popular component to prepare capsule shells • Gelatin is prepared by the hydrolysis of collagen obtained from animal connective tissue, bones, skin, and sinew. • Type A • Type B
图上生 国生 Physicochemical properties of gelatin ©Size of shells ·Eight size:000,00,0,1,2,3,4,5 ·Bloom strength gives an indication of the firmness of Calculated fill weight (g)at Size Volume (32) powder density of 0.8 g/em' the gel 000 1.37 1.096 00 0.95 0.760 ·Viscosity 0.68 0.544 050 0.400 Be vital to the control of the thickness 3 037 0.296 0.30 0,240 of the cast film 021 0.168 0.13 0.104 国生一 国生一 Other components in shell of hard capsules ·Plasticizer Sealing and Self-locking closure ·Thicker Self-locking ·Colorant ·Band sealing ·Spot welding ·Opacifier ·Preservative ·Water 国生一 圈生 ©Shell manufacture ·Gelatin dissolution Oxygen permeation through size00 gelatin capsules ·Dipping Oxygen permeation rate (mL24 hr) ·Rotation Traditiceal nonlcking Locking" (not banded) e ·Drying ·Stripping ·Trimming Joining ·Sorting .Printing 2
2 Shanghai Jiao Tong University Physicochemical properties of gelatin • Bloom strength • gives an indication of the firmness of the gel • Viscosity • Be vital to the control of the thickness of the cast film Shanghai Jiao Tong University Other components in shell of hard capsules • Plasticizer • Thicker • Colorant • Opacifier • Preservative • Water Shanghai Jiao Tong University Shell manufacture • Gelatin dissolution • Dipping • Rotation • Drying • Stripping • Trimming • Joining • Sorting • Printing Shanghai Jiao Tong University Size of shells • Eight size: 000, 00, 0, 1, 2, 3, 4, 5 Shanghai Jiao Tong University Sealing and Self-locking closure • Self –locking • Band sealing • Spot welding Shanghai Jiao Tong University Oxygen permeation through size 00 gelatin capsules
国必生 国生 Automatic filling machines The filling of hard gelatin capsules ·Auger fill machines 队 ·Rectification Vibratory fill machines Separation of caps from bodies Piston-tamp machines Dosing of fill material Dosing-disc machines ·Dosator machines Replacement of caps and ejection of filled -e-400--g-g-3 0 圈卢_Manufacture of Hard Capsules 国生 ©Powder filling General considerations of powder formulation ·Lubricity ·Choice of shell ·Flowability Power filling ·Compactibility .Sealing 圆政丛建 圈生 Manual Filling Machines ©Nonpowder filling ·Beads/pellets ·Microtablets ·Liquid 3
3 Shanghai Jiao Tong University The filling of hard gelatin capsules • Rectification • Separation of caps from bodies • Dosing of fill material • Replacement of caps and ejection of filled capsules Shanghai Jiao Tong University Manufacture of Hard Capsules Powder filling •Choice of shell • Power filling • Sealing Shanghai Jiao Tong University Manual Filling Machines Shanghai Jiao Tong University Automatic filling machines • Auger fill machines • Vibratory fill machines • Piston-tamp machines • Dosing-disc machines • Dosator machines Shanghai Jiao Tong University General considerations of powder formulation • Lubricity • Flowability • Compactibility Shanghai Jiao Tong University Nonpowder filling • Beads/pellets • Microtablets • Liquid
图生 图上人生 Soft Capsules ④Storage and package Disadvantages of soft capsule .Temperature Unsuitable for some kinds of drugs ·Humidity Specialized manufacturing equipment Trace aldehydes requirements. Higher manufacturing cost as compared to tablets Stability concerns with compounds susceptible to hydrolysis. 圈卢Soft Gelatin Capsules(softgels) 圈上生 ©Shell composition ·Gelatin Plasticizer:glycerin,sorbitol 8 ·Water 国垫生 Soft Capsules 圈生 Advantages of soft capsule Requirements of filling material Solidify the liquid drug Water content lower than 5% Improved bioavailability No low MW water soluble and volatile Enhanced drug stability organic compounds .Excellent dose uniformity No aldehyde Pharmaceutical elegance The pH of the liquids should be between 2.5 Superior patient compliance and 7.5 4
4 Shanghai Jiao Tong University Storage and package • Temperature • Humidity • Trace aldehydes Shanghai Jiao Tong University Soft Gelatin Capsules (softgels) Shanghai Jiao Tong University Soft Capsules Advantages of soft capsule • Solidify the liquid drug • Improved bioavailability • Enhanced drug stability • Excellent dose uniformity • Pharmaceutical elegance • Superior patient compliance Shanghai Jiao Tong University Soft Capsules Disadvantages of soft capsule • Unsuitable for some kinds of drugs • Specialized manufacturing equipment requirements. • Higher manufacturing cost as compared to tablets • Stability concerns with compounds susceptible to hydrolysis. Shanghai Jiao Tong University Shell composition • Gelatin • Plasticizer: glycerin, sorbitol • Water Shanghai Jiao Tong University Requirements of filling material • Water content lower than 5% • No low MW water soluble and volatile organic compounds • No aldehyde • The pH of the liquids should be between 2.5 and 7.5
国生 Soft Capsules 国上认连 ©The types of vehicles ©Enteric Capsules .Water-immiscible liquids The shell of enteric capsules is soluble in ·Vegetable oils intestine and insoluble in stomach .Aliphatic and aromatic hydrocarbons The content of enteric capsules is soluble in .Water-miscible,nonvolatile liquids intestine and insoluble in stomach ·PEG All liquids used for filling must flow by gravity at a temperature of 35C or less 国一 圈上生 Manufacture of softgels ·Rotary die process Evaluation of capsules Bubble method ·Appearance Weight variation ·Disintegration test ·Dissolution test ·Water content 国达建 国生 Learning Objectives Compatibility and stability concerns of softgels Shell composition of capsules Increased interaction due to intimate contact Size of hard capsule shells between the shell and its liquid contents Compatibility of drug and shell Loss of drug due to migration from vehicle Manufacture methods of soft capsules into the shell. 5
5 Shanghai Jiao Tong University Soft Capsules The types of vehicles • Water-immiscible liquids • Vegetable oils • Aliphatic and aromatic hydrocarbons • Water-miscible, nonvolatile liquids • PEG All liquids used for filling must flow by gravity at a temperature of 35℃ or less. Shanghai Jiao Tong University Manufacture of softgels • Rotary die process • Bubble method Shanghai Jiao Tong University Compatibility and stability concerns of softgels • Increased interaction due to intimate contact between the shell and its liquid contents • Loss of drug due to migration from vehicle into the shell. Shanghai Jiao Tong University Enteric Capsules • The shell of enteric capsules is soluble in intestine and insoluble in stomach • The content of enteric capsules is soluble in intestine and insoluble in stomach Shanghai Jiao Tong University Evaluation of capsules • Appearance • Weight variation • Disintegration test • Dissolution test • Water content Shanghai Jiao Tong University Learning Objectives Shell composition of capsules Size of hard capsule shells Compatibility of drug and shell Manufacture methods of soft capsules