The Top 5 Problems Encountered in Developing Your Formula for Tablets and Capsules
There are many factors and considerations that go into creating a pharmaceutical or nutraceutical product, which can prove to be a challenging test of trial and error. The formulation must be tailored to the characteristics of the active ingredient, whether it needs to be compressed into a tablet or encapsulated, and what type of excipients are needed to be used.
At LFA Machines, we know the consequences of formulation issues– it puts your time, product, and money at risk. We have connected with hundreds of customers over formulation development difficulties. Based on these customer interactions, we want to support others who find themselves in similar situations.
We’ve written a list of the top 5 obstacles and solutions that we have found you can run into when creating your solid dose formulation.
#1. Your formulation is too sticky
Sticky formulations can be a nuisance for both tablet presses and capsule fillers. When compressing a sticky formula, tablets may experience picking (product adheres to the punch tip’s logo, text, or design) or sticking (the formulation accumulates in the punch cup resulting in tablet defects). With encapsulation, a combination of a sticky mix building up on a capsule filler and its tooling with the machine operating at a high speed means:
- Inconsistent capsule weights
- Broken capsules
- Damaged machine
The first option for a fix is to slightly adjust your formulation. Adding a lubricant, such as magnesium stearate or stearic acid, to your formulation could help your product’s movement through the machine and any interactions with empty capsules. Another thing to check for is the environment in which you are tableting or encapsulating. Operate the machines in low humidity– a powder formulation can become sticky if it comes into contact with moisture in the air. Also ensure that the temperature does not exceed 75° or goes below 65°.
#2. Your formulation has poor flow
Flowability is how well your powder formulation transports through your tablet press or capsule filler. The particle sizes and shapes in your powder formulation can directly influence its flow properties, which in turn affects the quality of your pressed tablets or filled capsules. A formulation that has small dusty particles and a texture like powdered sugar will not flow well through a machine. Poor flow qualities in formulations can cause:
- Soft tablets
- Picking and sticking
- Inconsistent dosages
- Variations in capsule weights
Like with handling sticky formulations, incorporating excipients to your mix could help with poor flow. Dicalcium phosphate is a flow agent, which adds texture to a formulation due to its coarse particles. Dry lubricants also contribute to good flow. Magnesium stearate can reduce surface irregularities in the ingredients of the formulation, which reduces friction and encourages a more cohesive mix. Granulating the formulation may also prove to be beneficial; a dry granulator used in conjunction with a roller compactor or a wet granulator will produce more granules in your mix and reduce fines, allowing your product to flow smoothly through the tablet press or capsule filler.
#3. Your formulation isn’t soluble
Your powder mix’s solubility directly affects the bioavailability and efficacy of your product. Some active pharmaceutical ingredients (APIs) are inherently unable to dissolve in the stomach and can’t be absorbed. Due to its insolubility, the API dosage may need to be increased in a tablet or capsule, and that can come with some ramifications such as:
- Changes in procedures
- Increased costs
- Increased chances for inconsistent dosing
- Side effects and more
If your formulation is insoluble due to the API, there are several actions you can take. Both hard and soft gelatin capsules work well with transporting insoluble ingredients; whenever the capsule’s coating dissolves in the stomach, those ingredients are better able to be dispersed into the bloodstream. If you prefer your solid dose form to be tablets, you can use synthetic or natural binders that can assist with solubility. One option is LFA Machines’ all-in-one binder Firmapress. Other synthetic polymers like polyethylene glycol, polyvinyl pyrrolidone, and polyvinyl alcohol work by helping and prolonging tablet dissolution due to their hydrophilic characteristics, crystallized molecules, and solubility. Some natural alternatives to synthetic binders include starches, cellulose, carnauba wax, guar gum, pectin, and xanthan gum.
#4. Your formulation is too abrasive
Hard, coarse granules are commonly found in unrefined natural ingredients when manufacturing nutraceuticals like vitamins, minerals, and food supplements. Wear parts such as tablet press punches and capsule filler tamping pins are some examples of machine components that interact the most with a formulation. Because they come into high contact with the abrasive natural ingredients, they are at the most risk of degradation and damage over time. Damaged tooling can lead to:
- Other tablet defects
- Inconsistencies in capsule weights
- Halting operation due to changeovers
Typically, nutraceuticals are mostly made of APIs, leaving little room to actually change the formulation. The best approach to address a corrosive formulation is to purchase tooling that can handle it. High carbon, high chrome, and cold work tool steels are good examples of materials that can withstand a hard or abrasive formulation. It’s also recommended to apply special coatings to your punches and dies like hard chromium, which has anti-corrosive, anti-stickiness, and anti-wear properties. Complex, intricate punch tip designs will also find unfavorable conditions in most nutraceutical formulations; the coarse, granular natural ingredients need a more robust shape and form, so make sure to consider that when choosing your tablet design.
#5. Your formulation contains sensitive ingredients
You might notice that your formulation was working great one day– it was flowing and moving through the machine well and successfully compressed into consistently high quality tablets or tamped and filled into capsules, so later on you leave the remaining product out for the next round of production. The following day, the same formulation is caking to the machine and tooling, its flow properties are poor, and it won’t bind into a tablet or fill at the right weight in the capsule anymore. What could’ve happened?
When manufacturing solid dosage forms, one of the most important things to consider is the stability of the ingredients used. APIs such as L-arginine, chondroitin, mushroom powders, and minerals with chloride like magnesium chloride all have unstable, or sensitive, properties. Storage environmental factors such as temperature, exposure to light, and relative humidity can drastically affect not only powder formulations with sensitive ingredients, but also tablets, empty and filled capsules, and even machines. When hygroscopic ingredients are exposed to moisture, their particles and chemical composition can change. This can give rise to a shortened shelf life, lowered potency or degradation of the API, poor bioavailability, insolubility, broken tablets, brittle capsules, formulation sticking to the machine, and more problems.
It can be disheartening to perfect a formulation only for it to be ruined by something so easily preventable. Here are a few measures you can take if you find you have an unstable or sensitive formulation:
- Store formulation away from direct sunlight.
- Keep the temperature range between 65° - 75° Fahrenheit.
- Ensure the relative humidity measures between 35% - 65%.
- Add to the formulation excipients that combat humidity (e.g. microcrystalline cellulose, dicalcium phosphate, or silicon dioxide).
- Use HPMC capsules, which are resistant to moisture.
- Coat finished tablets with a thin polymer-based film.
- Securely package the finished tablets or capsules in something like bottles, canisters, or blister packs.
Developing a pharmaceutical or nutraceutical formulation can be complex, and you might encounter even more obstacles than the five we just mentioned– but we can help you find a solution.
We can work together to overcome your formulation development obstacles.
LFA Machines is happy to share with you that we offer formulation services for solid dose manufacturers. For up to 3 ingredients, with an additional charge per additional ingredient, we will conduct a variety of tests, as well as mix your ingredients and then perform those same tests on your formulation after mixing to create a working tablet to your specifications . If you have already perfected your formulation, we have a service for you, too: free proof of concept testing to analyze your mix as a tablet.
Reach out to a formulation expert today at https://www.lfatabletpresses.com/formulation-services or email our sales team at [email protected].