Pharmaceutical Dosage Forms and Drug Delivery Systems

Posted on May 13, 2024 in Biology

Factors Affecting Immunity

Phagocytosis

Phagocytosis is the process of engulfing bacterial mass, whether living or dead. The body cells responsible for this process are called phagocytes. There are two types of phagocytes present in the body:

1. Cells of the reticuloendothelial system
2. White blood cells

Antibody Production

Phagocytosis alone is not a reliable phenomenon for the destruction of pathogens. The body produces various other substances for protection, called antibodies. Antibodies are substances formed in the body in response to foreign proteins and certain other materials in the tissues. The materials that lead to antibody production are called antigens. There are three types of antibodies: Alpha, Beta, and Gamma. Most antibodies are gamma globulins compared to beta.

Injections (Parenterals)

Parenterals are sterile, pyrogen-free preparations intended for administration by injection into one or more layers of skin or mucous membrane.

Advantages

• An immediate physiological response can be achieved.
• Parenterals can be prepared to provide prolonged action.
• They are useful for unconscious patients.
• Parenteral therapy is very useful for treating uncooperative and nauseous patients.
• It provides 100% bioavailability.

Disadvantages

• Administration of dose must be carried out by a trained person.
• Painful administration
• Production cost of parenterals is high.
• Reversal of psychological effects is difficult once the drug is administered parenterally.

Calibration

Calibration is the measurement of a critical value of equipment function falling within the optimum range of its working.

Validation

Validation is establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes.

Types of Validation

1. Equipment Validation: To establish documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes. It is a regulatory requirement for cost reduction. Installation of new equipment, change of location, and modification all come under equipment validation.
2. Design Qualification: The instrument and its parts should be delivered as per the customer requirements in the purchase order. This should be done by the manufacturer or supplier before dispatching the instrument.
3. Installation Qualification: The instrument and its parts should be delivered according to the customer requirements in the purchase order. The facilities provided for installation should meet its specifications.
4. Operational Qualification: The newly installed equipment operates as per the manufacturer’s specifications. All functions should be operationally tested. For example, HPLC (High-Performance Liquid Chromatography).
5. Method Validation: Method validation provides a high level of assurance that a method will consistently yield results that are accurate, reproducible, and within the previously established specifications. To minimize product quality variations, different methods of preparation should be properly applied, starting from raw material to the finished product.

Premises for Manufacturing

The premises used for manufacturing should have separate areas for warehousing, packaging, labeling, and testing facilities. Proper drainage and waste disposal systems should be in place to avoid backflow and the entry of rodents, insects, or smoke.

Principles of Area of Premises

1. Ancillary Areas: Canteen, washrooms, cloth storage room, changing room.
2. Warehousing Area: Storage areas should have sufficient capacity to store various categories of materials and products like raw materials, packaging materials, bulk and finished products, released, rejected, and unused materials. All released, rejected, and unused materials should be stored in a locked area. Dispensing areas should be separate for active and raw materials.
3. Production Area: Laboratory area, packaging area.
4. Quality Control Area: Testing laboratories.
5. Quality Assurance
6. Drainage System
7. Disposal of Waste

Novel Drug Delivery Systems

Novel drug delivery systems are advanced drug delivery systems that improve drug potency, control drug release, and provide sustained therapeutic effects.

Classification of NDDS

1. Nanoparticles: Nanoparticles are particles ranging from 40-500 nanometers in diameter. They cannot be seen by the naked eye.
2. Microparticles: Microparticles are particles ranging between 0.5-200 micrometers. They are successful drug delivery systems that encapsulate both water-insoluble and sparingly soluble agents. Examples include microcapsules and microspheres.
3. Niosomes: Niosomes are vesicles of non-ionic surfactants incorporating cholesterol as an excipient. They are utilized for drug delivery to achieve desired therapeutic effects.
4. Liposomes: Liposomes are sacs of phospholipid molecules enclosing a water droplet, especially as formed artificially to carry drugs or other substances into tissues.
5. Phytosomes: Phytosomes are complexes of natural ingredients; they are single little cells.
6. Dendrimers: Dendrimers are highly ordered, branched polymeric molecules that are spherical in three-dimensional morphology.

Capsules

Capsules are solid dosage forms in which drug substances are enclosed in a gelatin shell.

Difference Between Hard and Soft Gelatin Capsules

Hard Gelatin Capsules

1. The hard gelatin capsule shell consists of two parts: body and cap.
2. They are cylindrical in shape.
3. The contents usually contain the medicament and a mixture of medicaments in powder or granule form.
4. Hard gelatin capsules are sealed after the drug is enclosed to prevent leakage.

Soft Gelatin Capsules

1. The soft gelatin capsule shell becomes a single unit after sealing the two halves.
2. They are available in round and oval shapes.
3. The contents usually consist of liquid or paste-like consistency.
4. Filling and sealing are done using machines.

Powders

A powder is a drug composed of solid, dry substances in finely divided particles used internally and externally.

Classification of Powders According to IP

Powders intended for external use can be specified according to the Indian Pharmacopoeia (IP):

• Coarse powders: All particles pass through sieve number 10 (1700 μm), but not more than 40% by weight pass through sieve number 44 (355 μm).
• Moderately coarse powders: All particles pass through sieve number 22 (710 μm).
• Moderately fine powders: All particles pass through sieve number 44 (355 μm).
• Fine powders: All particles pass through sieve number 85 (180 μm).
• Very fine powders: All particles pass through sieve number 120 (125 μm).
• Microfine powders: All particles pass through sieve number 350 (75 μm).

Ball Mill

A ball mill is used to grind materials into coarse or fine powders.

Principle

Ball mills work on the principles of impact and attrition, both responsible for size reduction. Rapidly moving balls reduce the size of brittle materials.

• Impact: Pressure exerted by two heavy objects.
• Attrition: Size reduction of materials when they collide with heavy balls.

Construction

• Cylinder: A hollow metal cylinder that rotates on its horizontal axis. It can be made of porcelain, metal, or rubber. The length is slightly greater than its diameter.
• Balls: Stainless steel balls inside the cylinder. The size depends on the cylinder diameter. Balls cover 30-50% of the cylinder’s volume.

Working

1. Open the lid and feed the material into the cylinder.
2. Introduce a fixed number of balls and close the lid.
3. Run the machine and adjust the speed as required.
4. After achieving the desired particle size, stop the machine and remove the material.

Double Cone Mixer

A double cone mixer, also known as a double cone blender, uniformly blends granules and dry powders.

Principle

Double cone blenders produce a homogeneous solid-solid mixture. The equipment moves the powder in different sections, providing complete mixing through its rotation speed.

Construction

The body consists of two cone-shaped sections joined to a central section. The rotational axis is perpendicular to the cone axis and passes through the central section. The blender body is held by two lateral supports, one fitted with the driving motor.

Working

1. The blender is attached to lateral supports to prevent movement during mixing.
2. Load the materials into the blender.
3. Close the lid.
4. Switch on the equipment, and the blender starts rotating in three directions: clockwise, anticlockwise, and straight.
5. After blending, open the lid and discharge the material.

Types of Tablets

1. Buccal or Sublingual Tablets: Designed to be kept under the tongue, these tablets release the drug, which is absorbed through the oral mucosa into the bloodstream. They provide a rapid onset of action compared to oral tablets, dissolving completely in about 15-30 minutes.
2. Lozenges: Intended to treat throat infections, these tablets dissolve in the oral cavity to prolong the duration of action. They do not require disintegrating agents, as dissolution is preferred over disintegration. They usually dissolve completely in about 15 minutes.
3. Solution Tablets: Designed to dissolve in a specified volume of fluid to produce a solution of a definite concentration.
4. Enteric-Coated Tablets: Coated with a material that resists dissolution in the stomach but dissolves in the intestine. This delays drug release.
5. Layered Tablets: Consist of two or more layers of materials compressed into a single tablet. Also known as laminated tablets, they are designed to mask drug incompatibility.
6. Time-Release or Prolonged-Release Tablets: Designed to provide medication over a longer period in a controlled manner.

Standards of Sieves

Common standards for sieves include:

• US standard sieve (USA)
• British standard sieve (UK)
• German standard sieve (Germany and Europe)
• IP standard sieve (India)
• International test sieve (worldwide)

Specifications of sieves used for pharmacopoeial testing:

• Sieve number: Sieve number 125 is commonly used according to pharmacopoeias.
• Aperture size: The distance between two wires.

Difference Between Flocculated and Deflocculated Suspensions

Coated and Uncoated Tablets

Coated Tablets

Tablet coating involves applying a coating material to the tablet’s surface to achieve desired properties compared to uncoated tablets.

Advantages of Coated Tablets

• Improved taste, odor, and color
• Easier swallowing

Uncoated Tablets

These are generally single-layer tablets prepared by direct compression of a single compound or granules.

Formulation of Tablets

Methods of Tablet Preparation

1. Direct Compression Method: Suitable for easily compressible powders containing both API and excipients.
2. Dry Granulation Method: Suitable for moisture- and heat-sensitive drugs.
3. Wet Granulation Method: Suitable for moisture- and heat-stable drugs.

Suspension

Suspensions are biphasic liquid dosage forms where finely divided solid particles (0.5-5 microns) are dispersed in a liquid medium.

Flavoring Agents

Flavor is a mixed sensation of taste that produces sensory perceptions for a substance.

Types of Flavoring Agents

Sweetening Agents

Sweetening agents mask the taste of formulations and impart a sweet taste.

Examples of Sweetening Agents

• Sucrose: Soluble in water, pH 4-8.
• Saccharin: Artificial sweetener.
• Aspartame: Artificial sweetener.

Organoleptic Properties

Organoleptic properties refer to color, sweetness, and flavoring agents.

Dosage Forms

• Creams: Semisolid dosage forms containing more than 20% water and less than 50% hydrocarbons, waxes, or polyols as vehicles.
• Suspensions: Heterogeneous mixtures where solid particles are spread throughout a liquid without dissolving.
• Lotions: Liquid, usually aqueous, medicinal preparations containing one or more insoluble substances, applied externally.
• Syrups: Medicines in the form of thick liquids containing sugar solutions.
• Liniments: Liquids rubbed into the skin to reduce pain or relieve stiffness.

Types of Immunity

Two types of immunity exist: active and passive.

• Active Immunity: Our own immune system protects us from a pathogen.
• Passive Immunity: We are protected by immunity gained from someone else.

Packaging Materials

Pharmaceutical packaging is an integral part of drug formulation and development. It requires standards to ensure the education, safety, and purity of pharmaceutical products.

Glass Containers

• Borosilicate Glass: Highly resistant and chemically inert.
• Treated Soda-Lime Glass: Commercially made soda-lime glass that has been dealkalized. Made with sulfur and mostly used in bottles. This type of bottle remains resistant for a long time.
• Regular Soda-Lime Glass: Used for parenteral preparations and exhibits better chemical resistance.
• Non-Parenteral: General-purpose soda-lime glass used for topical or oral products.

Plastic Containers

Metal containers

Advantages

Disadvantages