Gels | Topical Drug Products | Contract Manufacturing

OVERVIEW

Looking for contract manufacturing of gel drug products? Find CMOs, CDMOs offering GMP manufacturing services for topical gels on PharmaCompass.

Q1. What are topical dosage forms and what are the different types?

Topical semi-solid dosage forms are normally presented in the form of creams, gels, ointments, or pastes. They contain one or more active pharmaceutical ingredients(APIs) dissolved or uniformly dispersed in a suitable base with suitable excipients such as emulsifiers, viscosity-increasing agents, antimicrobial agents, antioxidants, or stabilizing agents.

Drug delivery systems administered via the skin are becoming progressively popular due to their convenience and affordability. The skin is the most important mechanical barrier to the penetration of many drug substances and acts as an ideal site to deliver a drug both locally and systemically.

There are several topical solutions available to treat surface wounds which apply directly to damaged tissue. Such formulations facilitate local action, act on the surface of the skin, exert their actions on the stratum corneum, or modulate the function of the epidermis and/or the dermis.

The medium used in formulating a topical semi-solid dosage form determines the product's consistency (dense and greasy or thin or watery) and whether the active ingredient stays on the surface or penetrates into the body. Vehicle choice depends on where to use the drug, aesthetic value, and ease of use.

Types of Topical Semi-Solid Dosage Forms:

Gels

Topical gel formulations are of increasing interest in the dermatology industry. Gel formulations are typically transparent or translucent, water-based semi solid dosage forms with good spreading properties and pleasing aesthetic characteristics.

Creams

Creams are emulsions of water and oil classified as oil in water (o/w) or water in oil (w/o) emulsions. O/W creams spread easily and do not leave the skin greasy and sticky, whereas W/O creams are greasy and more emollient. Medical cream formulations also contain suitable excipients such as emulsifiers and preservatives.

Lotions

Lotions are usually considered thicker than topical solutions and more likely to contain oil as well as water or alcohol. A lotion separates into parts with time so it needs to be shaken into a suspension before use. Lotions are easy to apply to large areas and are also suitable for application to hairy areas.

Ointments

Ointments are semisolid preparations intended for external application to the skin or mucous membranes. Ointments can be classified into four types depending on the carrier of the drug or base used for its formulation:

(1) Ointments with hydrocarbon or oleaginous bases

(2) Ointments with an absorbent or anhydrous base

(3) Ointments with an emulsion or water miscible base

(4) Ointments with water soluble bases.

Pastes

Pastes are mixtures of powder and ointments and are often defined as concentrated suspensions of oil, water and powder. The addition of powder increases the porosity of the topical formulation and also improves its consistency, which in turn increases the topical dosage form’s capability to adhere to the skin. Pastes can also be classified into the four categories listed above, for ointments.

At times, liquid products such as solutions and suspensions may be used as topical drug delivery systems. Besides liquid products, aerosol foams, sprays, solids (powders, suppositories) and transdermal patches may also be used to facilitate topical drug delivery. However, semi-solid dosage forms are the most common topical formulations prepared by contract manufacturers (CMOs, CDMOs).

Q2. What are gels and what are their advantages?

Topical drug delivery systems include a large variety of pharmaceutical dosage forms like semisolids, liquid products, sprays and solid powders, with semi solids being the most popular. The most widely used semisolid preparations for topical drug delivery include gels, creams and ointments.

Within the category of semisolid preparations, transdermal gels offer great potential for use in cosmetic and pharmaceutical fields. Due to the ever increasing use of novel penetration enhancement techniques, indications of gels for local action and the treatment of systemic diseases are expected to rise in the future.

Topical gels are semisolid drug delivery systems in which a liquid phase is constrained within a three dimensional polymeric matrix of natural or synthetic gum which has a high degree of physical or chemical cross linking. Medical gels are often used to achieve optimal cutaneous and percutaneous drug delivery.

Topical gels present an ideal candidate for a variety of applications due to their intermediate behavior between solid and liquid materials. Furthermore, gel formulations have better application properties and stability in comparison to medical creams and ointments.

Medical gels can be classified into the following types, amongst others:

- Organogels: Used in pharmaceutical preparations as well as cosmetics and food products.

- Hydrogels: Used as scaffolds in tissue engineering, contact lenses, sustained release drug delivery systems, etc.

- Xerogels: Used in formulating pharmaceutical drug delivery systems.

- Controlled release gels: Pharmaceutical gels in which active ingredients are absorbed by the body at a slower rate as compared to conventional dosage forms.

- Extended release gels: Gels in which the drug is released slowly over a longer period of time as compared to conventional dosage forms.

- Amphiphilic gels: Amphiphilic gels are able to dissolve certain poorly water-soluble drugs and exhibit both hydrophilic and lipophilic properties.

- Hydrophilic gels: These gels are hydrophilic, which means they are attracted to water molecules.

- Non aqueous gels: A non-aqueous gel composition comprising at least one anhydrous gel, at least one polymer, at least one ester, and at least one gelling agent.

- Bioadhesive gels: Such gels tend to adhere to or cause adhesion in living tissue. They stay in the GI tract longer, allowing more drug molecules to diffuse from it and be absorbed through the intestinal walls.

- Complexation gels: They have enhanced solubility which in turn increases the bioavailability of poorly water-soluble drugs.

Some Advantages of Gel Formulations:

- They can avoid gastrointestinal drug absorption difficulties caused by gastrointestinal pH.

- They can avoid enzymatic activity and drug interaction with food and drinks.

- They can substitute for oral administration, when the route is unsuitable.

- They avoid systemic and portal circulation following gastrointestinal absorption.

- Increased patient compliance as they are non-invasive.

- They can be formulated with advanced release profiles.

Q3. What are the steps involved in manufacturing gel drug products?

Gels are relatively easier to prepare when compared to ointments and creams. Medical gels contain gelling agents which provide increased viscosity, stability, body and improved suspension of added ingredients to aqueous solutions. In addition to the gelling agent, medicated gels contain active ingredients, antimicrobial preservatives, stabilizers, dispersing agents, and permeation enhancers.

Contract Manufacturing for Gel Drug Products - Steps:

Step 1. Raw Material Selection & Mixing Order Determination

Active pharmaceutical ingredients (APIs) eliciting desired therapeutic effects are chosen. Gelling agents, preservatives, stabilizers, antimicrobials & other excipients are also selected at this stage. Mixing order is determined and clearly defined, if the added ingredients affect the gelling process they are added after swelling and if not, they are added prior to it.

Step 2: Preparation of Gelling Medium

Purified water is the most widely used dispersion medium in the preparation of gels. Under certain circumstances, gels may also contain cosolvents or dispersing agents. While preparing the gelling medium care should be taken to avoid the evaporation or degradation of cosolvents.

Step 3: GMP Manufacturing of Gels

Medical gels can be manufactured in three ways:

- Cold Method GMP Manufacturing

During the cold method of manufacturing gels, water is cooled and placed in a mixing container. The selected gelling agent is slowly added to the container and agitated until a solution is formed. The active ingredient is then added in solution form, slowly with gentle mixing. Immediately, the medical concoction is transferred to another container and allowed to warm to room temperature, whereupon the liquid becomes a clear gel.

- Fusion Method GMP Manufacturing

During the fusion method of gel manufacturing, all or some of the components of a gel are combined by being melted together and cooled with constant stirring until congealed. Components that are not melted are added to the congealing mixture as it is being cooled and stirred.

- Dispersion Method GMP Manufacturing

The gelling agent is dispersed in water stirring at 1200 rpm for 30 minutes to create a gel and the active ingredient is dissolved in a non-aqueous solvent with added preservatives. The solution containing the drug is then added to the prepared gel with continuous stirring, thus producing a medical gel.

Step 4: Filling & Packaging

Once a gel is prepared it is filled into tubes, pouches, jars, etc. and sealed via automatic and semi-automatic equipment. It is further packaged in secondary packaging materials after which it is ready for distribution.

Q4. Which are the leading CDMOs & CMOs offering contract manufacturing for gel drug products?

Topical drug delivery systems are self-contained, discrete dosage forms that are designed to deliver drugs via intact skin or body surface routes of administration (transdermal, ocular, and intrauterine). Each of these systems is generally marketed in a single - unit soft blister pack or a preformed tray with a preformed cover or overwrap. Medical gels are the preferred semisolid dosage forms for formulations that facilitate topical drug delivery.

There are numerous CDMOs and CMOs offering pharmaceutical contract manufacturing for gel drug products. Some of the leading contract manufacturers offering pharmaceutical contract manufacturing and packaging for gel drug products are listed below.

Unither Pharmaceuticals

Unither Pharmaceuticals is a leading international CDMO which offers contract development & manufacturing services for various liquid & solid dosage forms.

Unither Pharmaceuticals also offers contract development and manufacturing services for various topical dosage forms including medical creams, gels, and ointments along with dry (tablets, powder, capsules) & liquid formulations (solutions & suspensions).

Polpharma

Polpharma provides a one-stop shop solution of vertically integrated services from API development to FDF formulation and contract manufacturing. Some of their facilities are specialized in providing pharmaceutical contract manufacturing and packaging services for ophthalmic drugs.

Polpharma offers customized contract manufacturing of creams and various other liquid and semi-solid dosage forms such as nasal drops and gels, eye drops, solutions and suspensions.

JGL d.d

JGL offers contract development and manufacturing for various semi-solid dosage forms such as gels, ointments, creams, soaps and lotions in the form of an aluminium or plastic tube. The filling process & packing is done by simply switching between different formats.

They offer pharmaceutical contract manufacturing and packaging services for solids and liquids as well as semi-solid dosage forms. Their semi solid contract manufacturing services are completely automated and the formulation process is thoroughly monitored. They also offer contract manufacturing of creams.

Madras Pharmaceuticals

Madras Pharmaceuticals offers contract manufacturing of creams along with tablets, capsules, dry powder for suspensions, liquid products, lotions, ointments, etc. Improved drug delivery systems with sustained release, instant release, bi-layered, tri-layered, etc. release profiles can also be achieved.

Madras offers contract manufacturing services for liquid orals (syrup, suspension, solution, micro-emulsion), external semisolids (cream, gel, ointment, lotion), medicated dusting powders, powder for injections, etc.