Capsules

Capsules

"Solid dosage forms in which the active ingredients are sealed in a hard or soft shell made of gelatin or other substances (starch, HPMC)"-USP

Selecting the capsule size

-Done during product development or extemporaneous filling -Depends on dose, density & compaction characteristics of drug & excipients -Use of the smallest size capsule, properly filled, is preferred.

Disadvantages of Capsules

-Hygroscopic drugs (e.g., KCl) and drugs with bound moisture cannot be formulated. -Generally more expensive than tablet dosage form -Soft or brittle hard gelatin shells (inappropriate humidity)

Capsule filling

-Punch method‐Extemporaneous filling of a small number of capsules -Accurate weighing method‐Granules can also be accurately weighed and poured in capsule. -Hand‐operated filling machine‐Regular or extensive filling in pharmacy, 24‐300 capsules at a time

Heat welding

-Sealed through a heat welding process that fuses the cap to the body through the double wall thickness at this juncture -In extemporaneous preparation, capsules may be sealed by lightly coating the inner surface of the cap with a warm gelatin solution immediately prior to placement on the filled capsule body

Lactose

example of most used diluent

Weight variation test

Capsule Evaluation: HGC‐Contents of 10 capsules are weighed individually. SGC‐Gross weight of 10 intact capsules is determined individually. Each capsule is cut open and the contents are removed using a suitable solvent. Solvent is evaporated. Empty dried shell are weighed and the net content of each capsule is calculated from the difference. Result must follow USP.

Dissolution test

Capsule Evaluation: Rate of drug getting dissolved SGC and HGC have the same method and requirements as that of uncoated plain tablets (will be discussed later) If the shells interfere with the analysis, shells can be removed for this test

Disintegration test

Capsule Evaluation: Time for capsule content to disintegrate SGC and HGC have the same method and requirements as that of uncoated plain tablets (will be discussed later)

Content uniformity

Capsule Evaluation: Nine out of 10 tested capsules should have drug strength in the range 85‐115%. None should fall outside 70‐125% of the declared potency.

Gelatin solubility

Cold water‐Insoluble but soften Hot water‐Soluble Warm gastric juice‐Soluble

Lubricants

Enhances flow properties e.g. Mg‐stearate, SiO2, talc

Hard gel capsule preparation

For both small and large scale production -Preparing the formulation -Selecting the capsule size -Filling the capsule shells -Capsule sealing (optional) -Cleaning & polishing of filled capsules

Advantages over Solid Dosage Forms

More elegant Generally better bioavailability Versatile (can carry liquid, semisolid or solid drugs) Easily prepared extemporaneously Easily protected from light (opaque shell)

Advantages over liquid dosage forms

More stable and therefore, longer shelf‐life Accurate dosing (because single unit) Easier transport and storage Taste masking is easier Easy identification by colored, embossed or imprinted shell Efficient and more productive manufacture, less packing cost

Gelatin safety

Non‐toxic, acceptable worldwide

Capsule filling machine

Performs all the operations needed to prepare capsules at a rate up to 180,000 caps/hr ‐Separates caps & bodies ‐Fills the body, replaces the caps ‐Seals the capsules (if needed) ‐Cleans outside

Types of formulations

Powder/granule , pellet, semi‐solid or liquid Capsule (capsule in capsule), tablet (tablet in capsule) Capsule/tablet in capsule can be effectively used in extemporaneous filling.

Cleaning & polishing

Small scale: Cleaned manually by cloth, NaCl Large scale: Machine (vacuum, NaCl)

Soft Gelatin Capsules

Softgels, containing liquid or semisolid matrix inside one piece of gelatin shell

Types of formulations of Soft Gelatin Capsules

Solutions, suspensions, paste, dry powder, and chewable softgels The whole manufacturing process are done by a single machine

Gelatin stability

Stable in air in dry state Prone to microbial decomposition if moist

Diluents

Useful for low dose drug to fill the volume Also offers cohesion to the powders LACTOSE, starch, microcrystalline cellulose

Disintegrants

Assist the breakup and distribution of the capsule contents in the stomach e.g. Pregelatinized starch

Preparation of formulation

General formulation properties for an ideal dosage form Ease of filling Proper blending of drug and excipients. Special care is needed for low dose drugs

Standard

Hard Gelatin Capsules: Capsule body enters inside capsule cap. Lacking many features

Coni‐snap Supro

Hard Gelatin Capsules: Have all features of Coni‐snap® The cap extends so far over the body that only the rounded edge of the latter is visible. Opening of such a filled capsule is difficult because the lower surface offers less gripping surface to pull the two halves apart. This increases the security of the contents and the integrity of the capsule (tamper‐evident)

Coni-snap

Hard Gelatin Capsules: Locking grooves (like Snap‐fit®) ensure proper closing of the rims of the filled capsules. Slightly tapered body reduces the risk of capsule rims touching on joining and essentially eliminates splitting and denting (by an average of 88%). The dimples prevent premature opening of the capsule.

Snap-fit

Hard Gelatin Capsules: Two halves positively joined through locking grooves around the shell walls. The two grooves fit into each other and ensure reliable closing of the filled capsule. It also eliminates accidental opening of the shells. Problem (with standard & Snap‐fit®)‐ High speed of capsule machine causes splitting (telescoping) and/or denting of capsule shell with the slightest contact between the two rims when they are joined.

Polycap

Hard Gelatin Capsules: ‐Five‐in‐one polypill that has moderate levels of five different medications in a single, one‐a‐day pill intended to reduce heart attacks and strokes ‐Contains three blood pressure medications (a diuretic, an ACE inhibitor, and a β‐blocker), a statin, and aspirin

Capsule size

Human use ranges from 000 (largest size) to 5 (smallest size)

Advantages of Soft Gelatin Capsules

Improve drug absorption, and patient compliance Safety of the operator from potent cytotoxic drugs Oils and low melting‐point drugs Dose uniformity for low dose drugs Product stability

Wetting agents

Increases dispersion of powder in GI fluid e.g. Glycerin

Capsule sealing

Kapseals®‐Tamper‐evident capsules, sealed joint (band) between the cap & the body

Hard Gelatin Capsules

Made of gelatin, sugar and water Gelatin obtained by the partial hydrolysis of collagen of the skin, white connective tissue, and bones of animals, along with sugar and water Titanium dioxide makes capsules opaque -Gelatin (starch or HPMC) -Water (13‐16%) -Color (FD&C and D&C dyes) -Opaquants (TiO2) -Sugar or other sweetening agent