Pharmaceutical Suspensions | Liquid Oral Stick Packs

Overview of contract manufacturers (CDMOs, CMOs) offering pharmaceutical suspensions & packaging solutions like liquid stick packs & liquid sachets.

Q1. What are pharmaceutical suspensions and what are the different types?

Pharmaceutical suspensions are heterogeneous systems consisting of two phases in which the internal phase (suspended particles) is dispersed uniformly throughout the external phase (suspension vehicle).

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 formulations such as solutions or syrups 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 may be required. The suspended particle diameter in the liquid oral dosage form usually ranges between 0.5 µm to 5.0 µm.

Amongst ready-to-use oral dosage forms, pharmaceutical suspensions are mostly utilized to achieve oral drug administration and are relatively more stable than solutions. Suspensions can be classified on the basis of the size of suspended particles, proportion of suspended solid particles, behavior of dispersed phase, etc.

Based on the route of administration, suspensions can be classified into:

- Oral suspensions

- Externally applied suspensions

- Parenteral suspensions

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 in which particle sizes are intermediate to those of suspensions and solutions. The size of the dispersed particles in colloidal suspensions do not exceed 1 µm.

Based on the proportion of solid particles, suspensions are divided into dilute suspensions and concentrated suspensions.

- Dilute suspensions are those where the concentration of suspension is not sufficient to cause significant displacement of water as they settle or particles will not be close enough for velocity field interference to occur.

- Concentrated suspensions have higher concentrations of suspended particles dissolved in the suspension medium (50%w/v solid).

Depending on flocculation behavior, supensions are divided into flocculated suspensions and deflocculated supensions.

- Flocculated suspensions have individual particles that are in contact with each other and form a network like structure.

- Deflocculated suspensions have individual particles that are not in contact with each other, the individual particles exist as separate entities.

Q2. What are oral suspensions and what are the benefits?

Oral pharmaceuticals are largely divided into solid and liquid dosage forms. Oral solids include tablets, effervescent tablets, capsules, powders, granules, orally dispersible films, etc. On the other hand, liquid oral dosage forms are available as syrups, solutions, suspensions, liquid sachets, dispersions, 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.

Suspensions are widely used liquid dosage forms. Pharmaceutical suspensions are dispersions of insoluble solid particles in a liquid medium; the internal part consists of particulates that are essentially insoluble but uniformly dispersed through the continuous phase with the aid of a suspending agent.

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. 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.

Some other advantages of oral suspensions include:

- Effective dispensing of hydrophobic drugs

- Faster absorption

- Avoidance of the use of cosolvents

- Taste masking of bitter drugs

- Controlled or sustained drug release

- 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

Q3. What are the steps involved in manufacturing oral suspensions?

A good understanding of the fundamentals of dispersion systems is essential for the pharmaceutical development and clinical and commercial manufacturing of suspension dosage forms. Various CDMOs and CMOs carry out the following steps for the clinical and commercial manufacturing of oral suspensions:

Step 1: Selecting raw materials

Excipient selection is one of the most important steps in oral suspension drug product development & manufacturing.

Step 2: Regulating particle size distribution

The particle size distribution in suspension development and manufacturing is a critical parameter that significantly impacts the bioavailability and pharmacokinetics of the product.

Step 3: Process of Manufacturing Suspensions

1. Suspensions are prepared by grinding or levigating insoluble ingredients in a mortar to make a smooth paste with a vehicle containing the wetting agent.

2. All soluble ingredients are then dissolved in the same portion of the vehicle and added to the smooth paste created in step 1, to get a slurry.

3. The slurry is then transferred to a graduated cylinder and the mortar is rinsed with successive portions of the vehicle.

4. The vehicle containing the suspending agent (or) flocculating agent is then added to the slurry.

5. The dispersion is made up to the final volume and a suspension is thus prepared.

Step 4: Analytical development

Analytical development includes tests for characterizing a suspension formulation and is important for further development and troubleshooting.

Step 5: Scale Up

Scale up is generally defined as the process of increasing batch sizes. In suspension scale-up, a formula is transformed into a viable, robust product by the development of reliable and practical methods of pharmaceutical manufacturing that affect the orderly transition from laboratory to full-scale production. It must include a close examination of the formula to determine its ability to withstand an aggregation of batch-scale and process modification concerns.

Step 6: Packaging

Suitable pharmaceutical packaging materials are subsequently selected. The pharmaceutical packaging presentation of liquid oral dosage forms is a critical step in maintaining chemical and physical stability, compliance, adherence, and facilitate proper handling by the target patient population, caregivers, and health-care professionals

Step 7: Regulatory compliance

All of this formulation design and drug product development work should ultimately culminate into a regulatory filing in accordance with regulatory guidelines for the suspension dosage form.

Q4. What are liquid stick packs and what are their benefits in packaging of oral suspensions?

Stick packs are a type of flexible pouch suitable for food, drink, and medical packaging. The packs themselves are sealed on two shorts ends and have a seal down the back. Stick packs can be emptied almost completely, easily consumed and transported, and are eco-friendly making this type of packaging increasingly popular with consumers.

They require 10 % – 40 % less packaging material than equivalent rectangular or square pouches. The above given qualities make liquid stick packs ideal for geriatric and pediatric formulations, as well as specialist dosage forms.

Stick packs are available for solid and liquid dosage forms:

- Liquid Stick Packs: Amongst oral dosage forms, liquid stick-packs for oral liquids and suspensions appeal to consumers with modern and active lifestyles. Liquid stick packaging further promotes accurate dosing and patient compliance, ideal for pediatric formulations and geriatric applications. Furthermore, liquid stick packaging is the new trend in the packaging of ready to use single unit dosage forms that are ideal for small and medium doses (filling quantity 10 to 15 ml).

- Powder Stick Packs: Powder stick-pack forms contain dry powder suspensions for oral use. Powder stickpacks serve as alternatives to drugs in capsules, tablets and sachets. Powder stick packs are easy for patients to carry and use and can be taken directly or can be diluted in food or drinks. Furthermore, powder sticks packs act as novel substitutes for patients with swallowing difficulties. Along with stick packs, sachet presentations are also suitable for dry powder suspensions intended for constitution into separate containers.

Stickpack contract packagers having multi-lane packaging provide a wide variety of powder and liquid stick packaging of various sizes and configurations for suspensions. Generally, they take the form of a small pouch, packet, or tube made from a flexible film, so that they are easily opened, portable, and can be consumed virtually anywhere.

The product is typically prepared for direct consumption and provides the complete recommended dose in a single serving. There are various contract manufacturers such as CMOs offering contract manufacturing for oral suspensions in liquid stick packs. Stick Pack contract packagers offer all types of products, including dry and liquid suspension. Stick Pack contract packaging manufacturers can produce up to thousands of stick packs per minute with the help of multi-lane packaging lines.

The advantages offered by liquid stick packaging include:

- Slim, compact, & an easy opening pour

- No spillage

- Unique, eye catching packaging which is good for branding

- Accurate dosing

- No wastage

- Eco-friendliness

- Customizability/Flexibility

Q5. Which are the leading CDMOs and CMOs offering manufacturing of suspensions?

There are various CDMOs, CMOs and other contract manufacturers offering clinical and commercial manufacturing for suspension.

Unither Pharmaceuticals

Unither has more than 25 years of experience in drug product development & contract manufacturing for oral suspensions (dry and liquid suspensions), liquid formulations such as solutions,, liquid stick-packs and liquid sachets (practical single-dose sachets), as well as solid and semisolid dosage forms.

Unither offers pharmaceutical contract manufacturing services for single unit dosage forms, practical single-dose sachets and delivery systems that can differentiate your products and grow market share by making them convenient, affordable, and easy to use. They offer contract manufacturing for oral suspensions along with Blow-Fill-Seal (BFS), liquid sachets, Unistick® liquid stick-packs, Unistick® powder stick packs, etc.

Quotient Sciences

Quotient Sciences is a global player in commercial drug product manufacture of small molecule products (oncology, orphan drugs). They offer pharmaceutical contract manufacturing services for solid and liquid dosage forms. Their commercial batch size capabilities for solid oral dosage forms is up to 500kg & up to 350L for liquid dosage forms.

They offer contract manufacturing for oral suspensions. Their drug product development capabilities include solutions, liquid suspensions, tablets, capsules, parenterals and solubility enhanced dosage forms.

Neuraxpharm

Neuraxpharm offers the development, manufacture and control of generic pharmaceutical specialties, both for Neuraxpharm and other laboratories, performed at their Lesvi facilities in Sant Joan Despí (Barcelona), Spain. They have expertise in pharmaceutical contract manufacturing for oral suspensions.

Softigel Procaps

Softigel is a contract manufacturer having expertise in pharmaceutical manufacturing for various drug delivery forms such as liquid suspensions, syrups, drops, emulsions, etc.

They offer pharmaceutical contract manufacturing services for solutions and suspensions in ampoules, ophthalmic droppers, vials and prefilled syringes.

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