Pharmaceutical Drug Dosage Forms III PPC 301 Fall 2022-2023 Lecture 6 PDF

# Pharmaceutical Drug Dosage Forms III ## PPC 301 ### Fall 2022-2023 ## Lecture (6) ## Capsules Dosage Form part II Prepared by D. Basant A. Abou-Taleb, M.sc., PHD Lecturer of Pharmaceutics & Ph. Technology Department Pharos University of Alexandria (PUA) # Soft Gelatin Capsules (SGC) 1. Composi...

# Pharmaceutical Drug Dosage Forms III ## PPC 301 ### Fall 2022-2023 ## Lecture (6) ## Capsules Dosage Form part II Prepared by D. Basant A. Abou-Taleb, M.sc., PHD Lecturer of Pharmaceutics & Ph. Technology Department Pharos University of Alexandria (PUA) # Soft Gelatin Capsules (SGC) 1. Composition of gelatin shell 2. Advantages of SGC 3. Filling of SGC 4. Pharmaceutical applications 5. Types of SGC 6. Factors affecting drug release 7. Quality control Tests ## SOFT GELATIN CAPSULES "SGC” * One piece, sealed capsules * "Softgels" or "Elastic Gelatin Capsules" * Addition of plasticizer resulting in a more flexible * Formulate single dose liquid-based formulations that provide a fast onset of action * Shapes of SGC is available, including round, oval, oblong, tubular and various miscellaneous shapes ## Materials of capsules - Gelatin - water - Plasticizer - Excipients ## 1. Plasticizing agents - Mechanical properties are controlled by the inclusion & concentration of plasticizers. - Polyhydric alcohols, such as glycerol or sorbitol or mixtures of these. - Concentration of plasticizer is 20-30% w/w of the wet mass. - Concentration >30% w/w will result in the capsule being too flexible. - Concentration <20% w/w will be too brittle ## Standard water content - During manufacture concentration of water is between 30-40% w/w of the wet mass. - After controlled drying capsule water content of 5-8% w/w. - Capsule over dried a brittle product ## 2. Miscellaneous excipients - SGC capsules may be colored or opaque, the chosen color(s) / opacifier being added during the manufacturing process. - e.g. Titanium dioxide used as an opacifier. - Flavoring agents may be also added to the capsule shell ## Anatomy of a Softgel - **SHELL:** - gelatin water - plasticizer - colors - flavors (aromas) - **FILL:** - oil solution - suspension - **Common suspending agents:** - lecithin, soybean oil, yellow wax - **Softgel surface can be printed on for easy identification** ## Advantages of SGC 1- Improved drug absorption 2- Easy to swallow 3- Avoids dust handling problems during manufacture and better operator safety 4- Overcome problems with manufacture (e.g. oils, low melting point drugs) as compressed tablet. 5- Dose uniformity for low-dose drugs 6- Good product stability (drugs are protected against oxidative degradation by gelatin shell). ## Soft Gelatin Capsules Filling - Lipophilic liquids - Water-miscible liquids - Self-emulsifying systems - Microemulsions & Nanoemulsions ## 1. Lipophilic liquids - Lipophilic liquids incorporate both vegetable oils (Soyabean oil) & fatty acid esters - Used as solvents of oil soluble drugs as vitamins A, D, E & K - Only a limited number of drugs are soluble in these materials and therefore, the formulation will either require the inclusion of co-solvents and/or surface-active agents - The fill may be formulated as a SUSPENSION (requiring the inclusion of viscosity-modifying agents and/or surfactants) ## 2. Water-miscible liquids - High-molecular weight alcohols, e.g. PEG 400, PEG 600 and non-ionic surface-active agents - The selected therapeutic agent may be dissolved SOLUTION or, if the solubility is exceeded - Dispersed within the solvent SUSPENSION which necessitate the addition of SAA or viscosity modifying agents to stabilize the formulation - Liquid vehicles (solvents) shouldn’t be volatile and must not migrate through the capsule shell. ## 3. Self-emulsifying Systems - Lipophilic liquids that contain a nonionic emulsifying agent (SAA). - Following release into the GIT tract, the fill material rapidly emulsifies into small droplets (with high surface area) and enhances the dissolution and hence absorption of the drug. ## 4. Microemulsions & Nanoemulsions - Matrices are encapsulated as "preconcentrates" - Preconcentrate fill matrix contains: - a lipid component & - one or more surfactant which spontaneously form a microemulsion or nanoemulsion on dilution with the GIT fluids. - If the dispersion phase droplet may be in submicron (microemulsion) or around 100 nm in size (nanoemulsion) ## Pharmaceutical Applications - A diagram of a circle is shown, with 5 parts: - Oral - Rectal - Chewable - Suckable - Twist off ## MANUFACTURE OF SGC ## "Rotary die process" - Dissolving the gelatin in water at 80° C under vacuum followed by the addition of plasticizer (as glycerol) - Addition of other components, such as colors, opacifier, flavors & preservatives - Supplying hot gel mass to the encapsulation machine through heated transfer pipes by a casting method that forms two separate gelatin ribbons - During the casting process the gelatin passes through the sol-gel transition and the thickness of each gel ribbon is controlled - Two gel ribbons are then carried through rollers (lubricated oil) to the rotary die encapsulation tooling - A diagram of the rotary die encapsulation tooling is shown - **H-hopper** - **Fill volume regulating valve ** - **segment** - **P** - **gelatin sheets** - **G** - **gelatin sheets** - **S** - **D** - **die rolls** - A diagram showing the factors affecting the capsule sealing process is shown - **Pressure** - **Shape & cutoff** - A diagram of the rotary die encapsulation tooling is shown - **Temperature** - **Capsule sealing** - **Timing of dosing** - **Quantity of fill** ## TYPES OF SGC ## (NEW FORMS) ## A. Vegicaps Soft Capsules - Animal free capsules. - Vegicaps® Soft capsules shell is formulated using the following ingredients: - Modified starch / - Carrageenan / - Disodium phosphate/ - Glycerol and/or sorbitol / - Purified water ## Features & Benefits (Advantages) 1- Compatible with an extensive range of fill formulations. 2- Proven chemical and physical stability of the shell mass. 3- Capsule shell provides excellent protection for oxygen-sensitive fill ingredients 4- Capsules can withstand elevated filling temperatures without adversely affecting the capsule quality this allows highly viscous liquids and semisolids to be successfully encapsulated. 5- Capsule seals exhibit improved resistance to corrosive materials, minimizing the possibility of leakage. ## B. Seamless Gelatin Capsules - Apparatus consist of two concentric tubes: Medicament tube & surrounding outer tube (gelatin solution). - Medicament issues from the tube surrounded by gelatin forming a spherical drop. - This is insured by allowing the drop to form in liquid paraffin in gelatin is insoluble. - The capsules are subsequently degreased & dried. - A diagram showing the process of how a seamless gelatin capsule is made is shown - **Seam Type** - **Seam-Less Type** - **Vibrator** - **Shell Sheets** - **Core Liquid** - **Die Rolls** - **Nozzle Jet** - **Flow control panel** - **Cooling oil** - **Capsules** ## Advantages of Seamless Capsules - Flexible adjustment of the dosage due to its reduced size (1-8 mm diameter) - Low shell ratio to content volume due to thin shell wall ## Formulation Factors Affecting Drug Availability From Capsules 1. The dissolution rate of the shell. 2. The rate of penetration of the dissolution medium into the powder. 3. The rate at which the powder mass deaggregates. 4. The amount and nature of adjuvant such as diluents, surfactant (if used). 5. Drug particle size. 6. The composition and characteristics of the capsule shell. ## Quality Control Tests Of Capsules 1- Content Uniformity 2- Weight Uniformity 3- Dissolution Testing 4- Disintegration Testing ## 1- Content uniformity - 30 capsules are selected and 10 of these are assayed individually. - At least 9 of these contain 85 - 115% of drug and none contain below 75-125% of drug. ## 2- Weight Uniformity: - All types of capsules and it is to be done on 20 capsules 1. Weigh an intact capsule. 2. Open the capsule without losing any part of the shell & remove the contents. 3. Weigh the shell. 4. The weight of the contents is the difference between the weighing. 5. Determine the average weight. ## Limit - Not more than two of the individual weights deviate from the average weight by more than the percentage % deviation shown in the table below & none deviates by more than twice that percentage | Average Weight of Capsule Content | % Deviation | |------------------------------------|---------------| | <300 mg | 10 | | ≥300 mg | 7.5 | ## 3- Disintegration Test: as in Tablets ## 4- Dissolution Test: as in Tablets except that the capsule is placed in the basket type - **Or** - metal coil (sinker) may be applied around the capsule (paddle method) ## Other requirements: 1. Content labeling. 2. Stability testing method. 3. Moisture permeation test. ## Content Labeling - Labeled to express the quantity of each active ingredient. ## Stability Testing - Long-term & Accelerated stability tests - Aim: suitable storage conditions & shelf life. ## Moisture Permeation - single unit dose containers packaging capsules ## Questions ## Thank You! ## LOGO