PRINCIPLES OF PHARMACEUTICAL FORMULATION AND DOSAGE FORM DESIGN:

Product Formulation Active Pharmaceutical Ingredient (API) is rarely administered solely as pure substance but almost always given in the form of dosage form. Dosage form is formulated invariably using drug and excipient(s) in appropriate proportions. Development of formulation with reproducible product quality is challenge for formulation scientist. For successful and quality formulation data generated from preformulation studies are important and give necessary platform. Selection of correct excipients in correct proportions is an important step in formulation development. Though excepients are defined as therapeutically inactive but it is a well established fact that they may interact with the API and other excipients in the formulation. This interaction reduces the effectiveness of dosage form. A good excipient must also be biocompatible. Based on already existing information about the excipients it is relatively easy for a formulator to select an appropriate excipient for the dosage form to be formulated.

Pharmaceutical Product formulation The process in which different chemical substances, drug(s) and excipients, are combined to fabricate a final medicinal product of a desired dosage form i.e. syrup, tablet, capsule, injectable liquid or powder etc. A dosage form is the physical form of a dose of a drug intended for administration or consumption. Pill, tablet, or capsule, liquid, aerosol or inhaler, liquid injection, pure powder or solid crystal etc. The route of administration for drug delivery is dependent on the dosage form of the substance in question.

GENERAL CONSIDERATIONS IN DOSAGE FORM DESIGN therapeutic matters as the nature of the illness, the manner in which it is treated (locally or through systemic action), Age anticipated condition of the patient.

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. For example, insulin cannot be given orally because being protein in nature it is extensively metabolized in the GIT before reaching the blood stream and is thus incapable of sufficiently reaching its therapeutic target destinations.

Some of well known incompatibilities are; Lactose and API’s with amine group in the presence of moisture and stearates resulting in the brownish discoloration of the tablet, this is called Mailard reaction. Tween 80 interacts with to a significant extent with methyl and propyl paraben to form complex. Eugdragrit interacts with acidic drugs e.g. diclofenac sodium. Some of the interactions are useful for instance, EDTA enhances the antibacterial activity of the benzalkonium chloride. Other vitally important factor is the processing parameters. The processing conditions and the time for which the formulation is subjected to a particular process must be well defined. The processing parameter may effect the API or the excipient or both. The light sensitive drug like Nifedipine, omeprazole etc , have to be manufactured in protected light environment. Hygroscopic drugs like clomtrimazole, cephradine , acarbose, penicillin's, ranitidine, norfloxacin etc. demand for stringent humidity control during formulation. Sterile dosage forms require aseptic conditions, stirring conditions must be controlled for emulsions and suspensions, autoclaving for heat sensitive API’s is not recommended for sterilization.

Optimization of both factors is essential for batch to batch reproducibility of quality dosage form. Stability of dosage form during shelf life is an essential requirement of quality dosage form. It must be kept in mind that a quality dosage form is not always commercially successful one. Cost, esthetic value and ease of administration are the other factors, which along with first two influence acceptability of the product to both prescriber and patient. The cost and esthetic value solely depends on the excipients and the formulation process adopted. Ease of administration/application depends not only on formulation but also on packaging

Need For Dosage Form Dosage Form: A dosage form actually act as vehicle for drug delivery. The form of the completed pharmaceutical product, e.g. tablet, capsule, injection, elixir, suppository. A dosage form is the physical form of a dose of medication. Principally a dosage form is formulated to achieve predictable therapeutic response of the drug included in the formulation. A vast majority of drugs are administered in milligrams amounts, much too small to be weighed but only on sensitive laboratory scaly. For instance how could the layman accurately obtain 325 mg of aspirin found in the common aspirin tablet from a bulk supply of aspirin, compare to other drugs the aspirin dose is too large fro example, the dose of ethinyl estradiol is 0.05 mg which is about 1/6500 the amount of aspirin or simply 6500 tablets of ethinyl estradiol is equal to the amount of aspirin found in single tablet. For such reasons it is proper to mixed the API with suitable excepients to give a physical form to deliver the drug. In addition to this the dosage form is needed for the following reasons.

For the protection of API form the destructive influence of the environment. 2. To conceal the bitter, salty or obnoxious taste or odor of API. 3. To provide liquid dosage form for API’s that are either insoluble or instable in the desired vehicle. 4. To provide liquid dosage form soluble in desired vehicle. 5. To provide extended drug release. 6. To provide optimal drug action from topical administration sites. 7. To provide for the insertion of a drug into one of the body cavity. 8. To provide drug directly into the blood stream. 9. To provide optimal drug action through inhalation therapy.

NEED FOR DOSAGE FORMS….. Safe and convenient delivery of accurate dosage To protect the drug substance from the destructive influences of atmospheric oxygen or humidity (coated tablets, sealed ampoules). To protect the drug substance from the destructive influence of gastric acid after oral administration (enteric-coated tablets). To conceal the bitter, salty, or offensive taste or odor of a drug substance (capsules, coated tablets, flavored syrups). To provide liquid preparations of substances which are either insoluble or unstable in the desired vehicle (suspensions). To provide clear liquid dosage forms of substances (syrups, solutions).

NEED FOR DOSAGE FORMS…… To provide rate-controlled drug action (various controlled-release tablets, capsules, and suspensions). To provide optimal drug action from topical administration sites (ointments, creams, transdermal patches, and ophthalmic, ear, and nasal preparations) To provide for insertion of a drug into one of the body’s orifices (rectal or vaginal suppositories). To provide for placement of drugs directly in the bloodstream or body tissues (injections). To provide for optimal drug action through inhalation therapy (inhalants and inhalation aerosols).