Overview of suspension liquid oral dosage forms: types, formulation development, applications, benefits, evaluation, and more on the excipients used, pharmaceutical technologies enabling oral drug delivery, primary packaging considerations, & liquid stick packs and single dose sachets.
Q1. What are the different types of liquid oral dosage forms?
Dosage forms are the means by which drug molecules are delivered to suitable sites of action within the body. They are classified according to their routes of administration into oral, topical, rectal, parenteral, ophthalmic, etc. and according to their physical form into solids, semisolids, and liquids. Among the various administration routes, oral dosage forms are usually the most convenient choice, their advantages include safety, good patient compliance, ease of ingestion, pain avoidance, and versatility to accommodate various types of drugs.
Oral pharmaceuticals are largely divided into solid and liquid oral dosage forms. While oral solids include tablets, effervescent tablets, capsules, solid & liquid sachets, powders, granules, orally dispersible films, etc. Liquid oral dosage forms and semi solids are available as syrups, solutions, suspensions, dispersions, semi-solids, softgels, etc. Liquid dosage forms are prepared by dissolving active pharmaceutical ingredients (API) in aqueous and nonaqueous solvents, suspending the API in appropriate mediums, or by incorporating the drug substances into oil or water phases. Various CDMOs are involved in the development of ready to use oral dosage forms including suspensions.
Linctuses, drops, gargles, mouth washes, & throat paints are some of the other oral liquid dosage forms available in the pharmaceutical industry. Liquid dosage forms offer certain benefits over other specialist dosage forms such as ease of swallowing, faster absorption, and more flexibility in dosing, however, they are more difficult to administer, harder to measure accurately, and have shorter lifespans as compared to other oral dosage forms.
Among solid and liquid oral dosage forms, pharmaceutical suspensions are the most widely used pediatric formulations. Besides oral drug delivery, liquids are also used for otic, dermal, parenteral, and optic drug delivery. When developing liquid forms, consideration is first given to the characteristics of the active drug. The major challenges in oral formulation development & manufacturing of liquid dosage forms are (i) the stability of a drug in a solution, (ii) the solubility of a drug at the required level, and (iii) acceptable taste.
Types of Liquid Dosage Forms for Oral Drug Delivery:
Syrups: They are viscous oral solutions that contain one or more active ingredients. The base contains large amounts of sugar such as sucrose or sorbitol, which can inhibit crystallization, or change the taste, base properties and/or modify solubilization.
Solutions: Oral solutions are clear liquid preparations for oral use containing one or more active pharmaceutical ingredients (API) dissolved in a suitable medium.
Elixirs: They are clear, sweetened hydro-alcoholic solutions intended for oral use and are usually flavored to enhance palatability. They are not as sweet syrups and are significantly less viscous than them.
Suspensions: In the development of ready to use oral dosage forms, Suspension is widely used liquid dosage form.They may be defined as preparations containing finely divided drug particles distributed somewhat uniformly throughout a medium in which the drug exhibits a minimum degree of solubility.
Q2. What is a pharmaceutical suspension and what are the benefits?
Pharmaceutical suspensions are dispersions of insoluble solid particles in a liquid medium (suspension vehicle). They are biphasic liquid dosage forms; the internal part consists of particulates that are essentially insoluble but uniformly dispersed through the continuous phase with the aid of a suspending agent and the external phase is generally aqueous, but may be an organic or oily liquid for parenteral drug delivery.
Ideally, the pH at which a drug is most stable would also be close enough to its solubility for delivering the desired dose in approximately 5 mL. Requiring patients to take more than 10 mL at a time may not be advisable because of lower patient compliance. In this scenario, oral formulation development for solution or syrup may be employed. However, if the pH at which a drug is most stable is not one at which there is enough solubility, a suspension formulation development may be required. The suspended particle diameter in the liquid oral dosage form development usually ranges between 0.5 µm to 5.0 µm.
In the development of ready to use oral dosage forms, pharmaceutical suspensions are mostly utilized to achieve oral, parenteral, and external drug administration and are relatively more stable than solutions. Depending on the size of the suspended particles, suspensions are divided into two types; coarse suspensions and colloidal suspensions.
• Coarse suspensions are heterogeneous dispersed systems, in which the particles are larger than 1 µm. Coarse dispersions are characterized by relatively fast sedimentation of the dispersed phase caused by gravity or other forces.
• A colloid is a heterogeneous mixture whose particle sizes are intermediate to those of suspensions and solutions. The size of the dispersed particles in colloidal suspensions do not exceed 1 µm.
Advantages of Suspensions:
- Effective dispensing of hydrophobic drugs
- Avoidance of the use of cosolvents
- Taste masking of bitter drugs
- Achieve controlled/sustained drug release
- Offering resistance to degradation of drugs due to hydrolysis, oxidation or microbial activity
- Efficient intramuscular depot therapy.
- Higher rate of bioavailability: Solutions > Suspensions > Capsules > Compressed tablets
- Easy swallowing for young or elderly patients
In case of pediatric formulations, oral dosage forms are divided into two main product categories:
(1) A ready to use oral dosage forms such as a tablets,effervescent tablets, syrups, solutions, or suspensions
(2) A formulation that requires manipulation such as a powder for constitution to a suspension or solution, effervescent tablets, dispersible tablets, bulk oral granules or powder to be dusted on food, and sprinkle capsules filled with pellets, granules, or mini tablets to mix with food or drinks.
Pharmaceutical suspensions are ready to use oral dosage forms that have been used for decades as the preferred dosage form for oral drug delivery to children. Although solid oral dosage form development includes the development of orally disintegrating tablets and dispersible tablets have some advantages as pediatric formulations in terms of stability, oral liquids as specialist dosage forms provide the clear advantage of flexible dosing, which is particularly important for highly active compounds with a narrow therapeutic window.
The major challenges in the development of ready to use oral dosage forms are (i) the stability of a drug in a solution, (ii) the solubility of a drug at the required level, and (iii) acceptable taste. The disadvantages of oral suspensions is that its high viscosity retards drug absorption, hinders the re-dispersibility of sediments, and creates problems in handling materials during bulk manufacturing.
Q3. What does the formulation development of oral suspension entail?
Suspension Oral Formulation Development:
A good understanding of the fundamentals of dispersion systems is essential for the pharmaceutical development of suspension dosage forms. Various CDMOs carry out the following steps for oral formulation development of suspensions:
1. Selecting compatible excipients: Excipient selection is one of the most important steps in oral suspension formulation development & manufacturing.
2. Regulating particle size distribution: The particle size distribution in suspension formulation development is a critical parameter that significantly impacts the bioavailability and pharmacokinetics of the product.
3. Analytical development: Analytical development services include the tests and instruments which are used to classify and characterize a suspension formulation.
4. Scale up: Scale up is generally defined as the process of increasing batch sizes