Semi-Solids: Don’t Underestimate the Potential (or the Challenges)

Semi-Solids: Don’t Underestimate the Potential (or the Challenges)

 

For decades, the most popular form of drug dosage has consistently remained oral solids —the tablet, the pill, the capsule. This trend is likely to continue, but the oral solid’s unassuming younger sibling – the semi-solid dose (SSD) – is making some noise. The semi-solids market is growing, and will continue to grow, over the next 5 years and beyond.

Don’t Underestimate the Semi-Solid Dose (SSD)
As the global population ages, we’ll see an increase in the demand for SSDs or topical drugs. And as drug companies innovate, the semi-solid dose will fill needs that other forms cannot.

However, the semi-solid form is not without its challenges, especially when it comes to scaling and manufacture. It is critical that companies with SSDs in their pipelines avoid underestimating the development & commercialization complexities of this dosage form. As the SSD market grows, so will the need for companies that know how to handle the specific technical challenges of this form.

Defining Semi-Solids
Before we further explore the growth trajectory and potential of semi-solids, let’s define the category. Semi-solid dosage forms are administered topically, coming in the form of creams, ointments, gels, and pastes. The active drug ingredient penetrates the skin surface, or in some instances, the eyes, nasal cavity, or cheek. SSDs are composed of oil and water.  According to cGMP compliant manufacturing and production conditions, semi-solid pharmaceutical drug products are smooth to the touch, don’t irritate the skin, typically have a pleasant scent, are applied easily, and are cosmetically elegant. They should minimize dehydration and grittiness.

In addition to the more traditional topical form, semi-solids can also come in the form of suppositories inserted into the body either vaginally or rectally. Body temperature dissolves the suppository exterior, allowing the active pharmaceutical ingredient (API) to be absorbed by surrounding tissue. It is a surprisingly strong niche. We typically see a good number of annual and new client requests for suppositories.

Semi-solids can also come in the form of a chew, another staple request for us. The semi-solid chew is ideal for patients who have trouble swallowing, pediatric patients or pets.

While LGM works with the spectrum of SSDs, chewables and suppositories are our forte. Plenty of CDMOs have the ability to manufacture semi-solids. But when it comes to suppository and chewable dosage forms, very few have LGM’s well-established track record and state-of-the-art filling and sealing technologies.

Semi-Solids Lead the Topical Drug Market
Semi-solids had the largest market share of the topical drug market in 2019, ahead of transdermal products, solids, and liquids. According to a Markets and Markets report, the overall topical drug delivery market is projected to steadily increase over the next five years, reaching $129.8 billion in 2025, up from $95.2 billion in 2020.

Demand for semi-solid topical drugs is strong because they are easy to administer and have limited side effects, which improves patient adherence. Patients and clinicians also like that the drug is applied directly to the affected area and that they avoid first-pass metabolism, as can happen with ingested forms. The ability of SSDs to cover a wide variety of drug molecules also makes them a popular option.

Given the ease of use, the affordability, and the high level of patient compliance, it’s no surprise the home care segment had the largest share of the topical drug delivery market in 2019.

As the population ages, the need for convenient at-home care will only increase, and semi-solid topical drug products will be a crucial part of that care. An Aging Population Means Growth for Semi-Solids
The home care segment is an important one. As the population ages, the need for convenient at-home care will only increase, and semi-solid topical drug products will be a crucial part of that care. Skin and eye diseases that accompany aging are becoming more prevalent, as is diabetes. Patients with diabetes often have related dermatological complications that require topical treatments.

The high prevalence of skin and soft tissue infections and burns is also contributing to the rise of the semi-solid market. Asia Pacific is seeing a surge in skin disease, including skin cancer. That region is also seeing an increase in contraceptives, which has also impacted the semi-solids market. It’s worth noting that income levels in emerging markets are rising, allowing more patients access to all drug forms, not just semi-solids. Still, this is positive for the semi-solid market.

The rise in personalized medicine is also contributing to the growing interest in semi-solid forms. Companies are finding the semi-solid is the “ideal” vehicle for delivering customized dosages, created on an individual patient basis. Another factor is the increase in APIs that lack aqueous solubility. According to Contract Pharma’s article on Quality Factors Influencing Semi-Solid Manufacturing: “Developments in various dispersion techniques are producing positive results that in certain cases may be incorporated into semi-solid products.”

Challenges that Require Expertise
Despite being favorable among clinicians, patients, and drug-makers alike, the semi-solid drug form does have its challenges. Most of the difficulties occur in manufacturing and scaling, so experts suggest using an experienced CDMO throughout the process.

A study on manufacturing of semi-solid dosage forms in Scholars Academic Journal of Pharmacy (SAJP) made the following suggestion: “Outsourcing formulation development and manufacturing to a contract development and manufacturing organization (CDMO) is often recommended, as it allows technology transfer, scale-up, and manufacturing to take place at one location, which ensures project continuity.”

SSDs are complex products, which means that every step of the manufacturing process – transferring materials, mixing, degassing, filling, storing – can impact the product’s characteristics. For example:

  • If the wrong type of mixer is used, the particle size may be too large.
  • If proper care isn’t taken when introducing the active ingredients, the product’s efficacy may suffer.
  • If any entrapped air remains after the degassing/vacuuming step, product stability may be reduced.
  • If air is accidentally reintroduced during the filling phase, it could affect the release of the drug from the container.

Once manufacturing is complete, it’s essential that the product is stored appropriately and monitored for any issues, as even a slight change in conditions could compromise package integrity.

Scaling is particularly challenging for SSDs because of the differences in equipment at the bench and large-scale levels. Large scale mixers might be more powerful, but they aren’t as efficient. If you try to improve efficiency by increasing the speed, the product results may be different. The sheer sizCompanies are finding the semi-solid is the “ideal” vehicle for delivering customized dosages, created on an individual patient basis. e of the vessel may restrict flow or put pressure on the materials at the bottom, thus impacting homogenization. If the mixer cannot achieve proper uniformity, the product could produce an uneven distribution of the API and adverse effects.

Another variable that is difficult to replicate at a large-scale level is temperature. Improper temperature can drastically impact the product’s key elements, such as grittiness and spreadability. Extreme temperature may even influence microbial features, and the time it takes to heat or cool the product can also impact characteristics such as viscosity. However, manufacturers can lessen these concerns by using best-in-class equipment.

Not only is the proper equipment necessary, but a proper team is, too. The team must have the experience to understand the nuances of SSD manufacturing and the technical expertise to foresee and avoid any significant missteps. This is especially true now, as there has been a growing need for bigger batch sizes under tight timelines over the last few years. This shift has caused formulation teams to have a much larger role in scale-up engineering than ever before. Simultaneously, the FDA is looking more closely at Phase 3 or Q3 properties, the microstructure properties. These demands are why it’s crucial to have a team that has a history of manufacturing SSDs and that knows how the market has evolved.

The Equipment and Expertise Needed for Your Next SSD Project
Semi-solid doses may be quite challenging in the manufacturing and scaling phase, but proper equipment and an experienced team can make all the difference — and this where LGM comes in.

Our recent purchase of Nexgen has allowed us to offer clients the highest level of SSD manufacturing expertise, along with state-of-the-art equipment. Our experienced team has proudly been handling SSD challenges for decades, from challenging volumes of Blue Star Ointment in the 2000s to a pseudoephedrine product designed for limited extraction. Our unique fee-for-service and partnership/risk-profit-sharing model allows us to provide personalized service to each customer.

The demand for semi-solids is only going to grow. As the global population ages and companies continue to innovate, the need for SSDs will increase, and the market will evolve, and we will be there.

Contact us to discuss your potential project.

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