Dosage form Part 1

Dosage form

Dosage forms are pharmaceutical ingredients that are masked in order to be used.

Dosage form is a mixture of active drug components and nondrug components which is called excipients,  Capsule shell which is considered as non-reusable material is used either as ingredient or packaging .When each drug product is individually packaged, the term unit dose can also sometimes encompass non-reusable packaging as well.

The term dosage form can also sometimes refer only to the chemical formulation of a drug product's constituent drug substance(s) and any blends involved, without considering matters beyond that (like how it's ultimately configured as a consumable product such as a capsule, patch, etc.). Because of the somewhat vague boundaries and unclear overlap of these terms and certain variants and qualifiers thereof within the pharmaceutical industry, caution is often advisable when conversing outside of one's typical discourse community.

Depending on the method/route of administration, dosage forms come in several types. These include many kinds of liquid, solid, and semisolid dosage forms. Common dosage forms include pill, tablet, or capsule, drink or syrup, and natural or herbal form such as plant or food of sorts, among many others. Notably, the route of administration (ROA) for drug delivery is dependent on the dosage form of the substance in question. A liquid dosage form is the liquid form of a dose of a chemical compound used as a drug or medication intended for administration or consumption.

Various dosage forms may exist for a single particular drug, since different medical conditions can warrant different routes of administration. For example, persistent nausea and emesis or vomiting may make it difficult to use an oral dosage form, and in such a case, it may be necessary to utilize an alternate route such as inhalational, buccal, sublingual, nasal, suppository or parenteral instead. Additionally, a specific dosage form may be a requirement for certain kinds of drugs, as there may be issues with various factors like chemical stability or pharmacokinetics. As an example, insulin cannot be given orally because upon being administered in this manner, it is extensively metabolized in the gastrointestinal tract (GIT) before reaching the blood stream, and is thereby incapable of sufficiently reaching its therapeutic target destinations. The oral and intravenous doses of a drug such as paracetamol will differ for the same reason.



Types:

Oral:

• Pill, i.e. tablet or capsule
• Specialty tablet like buccal, sub-lingual, or orally-disintegrating
• Thin film (e.g., Listerine Pocketpaks)
• Liquid solution or suspension (e.g., drink or syrup)
• Powder or liquid or solid crystals
• Natural or herbal plant, seed, or food of sorts (e.g., marijuana such as that found in "special brownies")
• Pastes(Colgate)

Inhalational:

• Aerosol
• Inhaler
• Nebulizer
• Smoking (often in natural herb (e.g., tobacco, marijuana) or freebase powder form (e.g., cocaine, methamphetamine))
• Vaporizer (usually to vaporize natural herbs like marijuana)

Parenteral Injection:

• Intradermal (ID)
• Intramuscular (IM)
• Intraosseous (IO)
• Intraperitoneal (IP)
• Intravenous (IV)
• Subcutaneous (SC)
• Intrathecal (IT) Injection into the spinal column

Topical:

• Cream, gel, liniment or balm, lotion, or ointment, etc.
• Ear drops (otic)
• Eye drops (ophthalmic)
• Skin patch (transdermal)
• Vaginal rings

Suppository:

• Vaginal (e.g., douche, pessary, etc.)

Preformulation : A need for Dosage Form Design

The Concept of Preformulation:

It is essential that pertain fundamental physical and chemical properties of the drug molecule and other divided properties of the drug powder are determined before the development of the major dosage forms (Tablets , capsules or both of them). This information decides many of the subsequent events and approaches in formation development. This first learning phase is known as preformulation.

Definition:

Preformulation involves the application of biopharmaceutical principles to the physicochemical parameters of drug substance are characterized with the goal of designing optimum drug delivery system.

Before beginning the formal preformulation programs the preformulation scientist must consider the following factors :-

• The amount of drug available.
• The physicochemical properties of the drug already known.
• Therapeutic category and anticipated dose of compound.
• The nature of information, a formulation should have or would like to have.

Preformulation drug characterization in a structured program:

Test	Method/ function Characterization
Fundamental:
1) UV spectroscopy	Simple assay
2) Solubility	Phase solubility/ purity
a) Aqueous	Intrinsic & pH effect
b) pKa	solubility control , salt formation
c) Salt	Solubility, hygroscopicity & stability
d)Solvents	Vehicles & Extraction
e) ko/ w	Lipophillicity, structure activity
f) Dissolution	Biopharmacy
3) Melting point	DSC-polymorphism hydrate & solvent
4) Assay development	UV, HPLC, TLC
5) Stability
In Solution	Thermal, hydrolysis, pH
In solid state	Oxidation, proteolysis metal ion
Derived:
6) Microscopy	Particle size and morphology
7) Bulk density	Tablet and capsule formation
8) Flow properties	Tablet and capsule formation
9) Compression properties	Acid / excipient choice
10) Excipient compatibility	Preliminary screen by DSC, Conformation by TLC

UV Spectroscopy:

The first requirement of any preformulation study is the development of a simple analytical method for quantitative estimation in subsequent steps. Most of drugs have aromatic rings and/or double bonds as part of their structure and absorb light in UV range, UV spectroscopy being a fairly accurate and simple method is a performed estimation technique at early preformulation stages.

The absorption Co-efficient of the drug can be determined by the formula:

E =    AF / X 

Where ,            A = Asborbance

                        F = dilution factor

                        X = weight of drug (mg)

            It is now possible to determine connectration of drug in any solution by measuring absorbance.

            C =      AF / E mg/ ml

            Characterization of drug molecules is very important step at the preformulation phase of product development. Following studies are conducted as basic preformulation studies, special studies are conducted depending on the type of dosage form and the type of drug molecules.


1)         Solubility determination

2)         pKa determination

3)         Partition co-efficient

4)         Crystal properties and polymorphism

5)         Practical size, shape and surface area.

6)         Chemical stability profile.



Solubility Determination:

The solubility of drug is an important physicochemical property because it effects the bioavailabilty of the drug, the rate of drug resale into dissolution medium and consequently, the therapeutic efficiency of the pharmaceutical product.

The solubility of the molecules in various solvents is determined as a first step. This information is valuable is developing a formulation. Solubility is usually determined in variety of commonly used solvents and some oils if the molecules is lipophillic.  

The solubility of material is usually determined by the equilibrium solubility method, which employs a saturated solution of the material, obtained by stirring an excess of material in the solvent for a prolonged until equilibrium achieved :-

Common solvents used for solubility determination are:

• Water
• Polyethylene Glycols
• Propylene Glycol
• Glycerin
• Sorbitol
• Ethyl Alcohol
• Methanol
• Benzyl Alcohol
• Isopropyl Alcohol
• Tweens
• Polysorbates
• Castor Oil
• Peanut Oil
• Sesame Oil
• Buffer at various pHs

Dosage form Page 2

REFERENCE:

• http://en.wikipedia.org/wiki/Dosage_form
• http://www.pharmainfo.net/reviews/preformulation-need-dosage-form-design