Capsule Dosage Form PDF

Lec 5: Capsule Dosage Form  Capsules A solid dosage form in which the drug substance is enclosed within a hard or soft soluble shell generally formed from gelatin. Advantages: 1. It is easier than tablets to hide the undesirable...

Lec 5: Capsule Dosage Form  Capsules A solid dosage form in which the drug substance is enclosed within a hard or soft soluble shell generally formed from gelatin. Advantages: 1. It is easier than tablets to hide the undesirable test or smell. 2. Elegant looking and easy to swallow. 3. Uses a minimal amount of excipients and little compression is required during formulation. Capsules are classified into hard and soft gelatin capsules depending on the nature of the capsule shell. Soft cap. is made of more flexible, plasticized gelatin film than hard gelatin capsules. Difference: Soft gelatin capsules are made and filled/sealed in one process while the hard gelatin cap. are made and filled in two separate processes 2 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Capsule Shell Compositions Gelatin: Is the main component in the shell of both hard and soft gelatin capsules. Gelatin is obtained from hydrolytic extraction of Main Ingredients in Capsule Shell treated animal collagen. à There is No natural gelatin. Plasticizers Gelatin Its physical and chemical properties depend on the parent collagen, method of extraction, and pH value. Capsules Common sources of collagen are animal bones, hide portions, and frozen pork skin. Collagen from bones and skin are readily Other Ingredients (colors, available in commercial quantities. Opaquants, preservatives, water, …) 3 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Gelatin Synthesis Type A gelatin is derived from acid-treated precursors. Type B gelatin is from an alkali-treated precursor. Capsule shells can be made from either one. However, the best shell is the one that is made from a mixture of both. è Bones gelatin produces tough, firm film, but tends to be hazy and brittle. Skin gelatin contributes plasticity and clarity to the blend thereby reducing haze or cloudiness in the finished capsules. Not for save 4 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Gelatin The Main Specification required for gelatin is the Bloom strength. The bloom or gel strength of gelatin is a measure of the cohesive strength of the cross-linking that occurs between gelatin molecules and is proportional to the molecular weight of the gelatin. Bloom test is determined by measuring the weight in grams required to move a plastic plunger 4 mm deep into a 6.6% gelatin gel that has been gelled at 10 ˚C for 17 hrs. Bloom ranges from 150 to 250 g are acceptable. The higher the bloom strength of the gelatin used, the more physically stable the resulting capsule shell. The cost of gelatin is directly proportional to its bloom value. 5 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Alternate Capsules X Capsule shells can be made from materials other than gelatin for various reasons. That includes religious and vegetarian dietary restrictions. 1. Hydroxypropyl methylcellulose (HPMC): odorless, and flexible and their appearance corresponds to that of gelatin capsules, except that the surface of HPMC capsules is matt. HPMC is plant plant-derived material. 2. Starch Capsules: The capsule shell is made of potato starch and represents a direct alternative to hard gelatin capsules. 3. Pullulan capsules Biopolymer material. It is a Polysaccharide produced by the fermentation of carbohydrates (like starch/sugar) by the fungus Aureobasidium Pullulan. These are 100% natural vegetable capsules that are edible polymer, odorless & have no identifiable taste. 6 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Capsule Shell compositions Plasticizers: More common for soft gelatin capsules. The ratio of plasticizers to gelatin determines the hardness of the shell. Examples of materials used as a plasticizer are glycerin, sorbitol, and a combination of both. Additional components: Color, Opaquants, or materials such as methylcellulose and polyvinyl alcohols have been used to modify the solubility of gelatin or to produce an enteric capsule. The color of gelatin is important, especially for soft gelatin capsules. As a general rule: clear color is used for clear content and opaque colors are used with suspensions. Dark colors are more appropriate for large-size oral products since they will not accentuate the size. 7 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Hard Gelatin Capsules Hard capsules are preferred over tablets due to: 1. Easier to formulate because there is no requirement that the powders be formed into a coherent compact that will stand up to handling. 2. The capsule-filling process is easy and requires minimal strength. 3. Preferred to hide the undesirable taste and odor. 4. Easier to modify the release profile due to the limited factors involved. Disadvantage: 1. Capsule filling is much slower than the tablet press process. 2. Some drugs may cause irritation when suddenly released in the stomach (especially for extremely soluble compounds) 8 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Hard Capsule Shell Synthesis Include different steps: Dipping è Spinning è Drying è Stripping è Trimming è Joining https://youtu.be/IDtNhL7z06M 9 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Hard Capsule Shell Synthesis Dipping: Cold pins of a specified size are dipped into a hot gelatin solution of a controlled viscosity. Solution viscosity, rate, and time of dipping will determine the shell thickness. Both the cap and body are dipped at the same time into a solution of similar viscosity. Spinning: Pins are rotated to distribute the gelatin uniformly during which time the gelatin is gelled by a blast of cool air. Drying: The pins are moved through a series of controlled air-drying kilns (oven) for the gradual and precisely controlled removal of water. 10 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Hard Capsule Shell Synthesis Stripping: The capsules are stripped from the pins. Trimming: Capsules halves are trimmed to exact length. Finally, the capsule halves are joined to each other and ejected from the machine. The thickness of the capsule wall is controlled by 1) the viscosity of the gelatin solution and 2) the speed and time of dipping. The capsule body and cap are joined to each other by a coin-snap™ construction through locking grooves in the shell walls. This will ensure reliable closing of the filled capsules. 11 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Capsule Filling Machine Capsules can be filled with a wide range of pharmaceutical materials including powders, granules, tablets, capsules, paste, and non-aqueous and oily liquids. Capsule-filling machines work based on two feeding mechanisms: 1. Auger type (dependent): capsules are filled with loose powder. In this type, powder is transferred directly to the capsule body, and the flow of powder is aided by either a revolving auger or by vibrating plate. https://youtu.be/N5sGRiR4HZg?si=IbFoMDOJXFDePNKM 12 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Dosator Type filling machine Dosator type (independent): compressed the measured amount of powder to form a plug. https://youtu.be/XrZgRCWH3No 13 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Capsule Capacity The empty capsules are sold by size. The most commonly employed for human use range from size 000 (the largest) to size 5 (the smallest). Size 00 capsules may occasionally be used if the amount to be filled is large (capacity ~ 960 mg). Powder weights listed are approximate and vary with the amount of pressure employed in hand filling, or with the type of equipment utilized in machine filling. 14 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Finishing and Polishing Finished capsules from filling equipment require some type of dust removal and/or polishing before the remaining operations of inspection, bottling, and labeling are done. The following equipment is commonly used for this purpose: 1. Pan polishing: A piece of cloth is placed in the pan, and this cloth is used to trap the removed dust as well as to impart a gloss to the capsules. 2. Hand polishing: the capsules are rubbed with a cloth manually. This procedure imparts a somewhat improved gloss to the capsule. 3. Brushing: capsules are fed under rotating soft brushes, which serve to remove the dust from the capsule shell. 15 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form Soft Gelatin Capsules 16  Soft Gelatin Capsules (SGcaps) Solid dosage form containing liquid medication. They are formulated for oral, suppository, topical, and for cosmetic uses. As in a hard gelatin capsule, the shell of the capsule is composed of gelatin, water, and plasticizer. In addition, it may contain compounds such as preservatives, colors, and opaquing agents. The difference from hard gelatin capsules is the high amount of water which may constitute up to 50%. 17 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Advantages It offers the following advantages: 1. They permit liquid medications to become easily portable. 2. Uniformity of dosage because they contain liquid which is more uniform than powder. 3. The disintegration and dissolution rates are faster than that of other solid dosage forms. The bioavailability of drugs is often improved since these capsules contain the drug in liquid form. 4. Safer handling of highly potent or cytotoxic drug compounds. Disadvantage: It requires special equipment and skills to be formulated. 18 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Capsule Contents The content of soft gelatin capsules may be solution or suspension. Note: Only those liquids that are both water-miscible and volatile cannot be included as major constituents of the capsule content è because they can migrate into the hydrophilic gelatin shell and volatilize from the surface. (Water and ethyl alcohol fall into this category). However, up to 5%, water and alcohol can be used as minor constituents (e.g., as cosolvents to aid in the preparation of solution). 19 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form  Capsule Contents Preparations for encapsulation should have a pH between 2.5 and 7.5 because: 1. More acidic preparations can cause hydrolysis of the gelatin shell 2. Those that are more alkaline can tan the gelatin and thus affect the solubility of the shell. Solids are incorporated into the soft gelatin capsules as either a solution or suspension. 20 College of Pharmacy- Industrial Pharmacy II- 5th stage- First Semester Capsules Dosage Form