Excipient Impact on Drug Absorption

Overseen By Maureen Shin, PharmD, MS

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of California, San Francisco

Must not be taking: OATP2B1 substrates

Disqualifiers: Extreme obesity, Pregnancy, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how sodium lauryl sulfate (SLS), an ingredient often added to medicines, affects the body's absorption of a specific drug, fexofenadine. Researchers compare drug absorption in individuals taking the drug alone versus those taking it with low or high amounts of SLS. Healthy individuals who can avoid certain foods and supplements that might interfere with the study are suitable candidates. This study may interest those without allergies to the drug or SLS and who are comfortable avoiding certain fruit juices. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering a unique opportunity to contribute to foundational knowledge.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any drugs, especially those known as OATP2B1 substrates, except for birth control hormonal medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sodium lauryl sulfate (SLS) is often used in drug products and is generally safe. However, it can sometimes cause mild issues like sneezing or a sensitive airway, which might lead to coughing or breathing difficulties in some individuals. This doesn't happen to everyone, but it's something to keep in mind.

Fexofenadine, approved by the FDA for treating allergies, has a good safety record. Most people tolerate it well with few side effects. This study examines how SLS might affect the absorption of fexofenadine in the body. Previous studies have not reported any serious safety concerns when combining these two substances. Participants will take fexofenadine with either a small or large amount of SLS, or without it, to observe any differences. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different amounts of sodium lauryl sulfate (SLS) might affect the absorption of fexofenadine, a common antihistamine. Unlike standard treatments, which typically focus on the active ingredient alone, this study investigates how excipients like SLS can enhance drug absorption. By examining these variations, the study could reveal new ways to improve how quickly and effectively fexofenadine works, potentially leading to faster relief from allergy symptoms. This approach could pave the way for more efficient drug formulations, offering patients quicker and potentially more consistent results.

What evidence suggests that sodium lauryl sulfate affects drug absorption?

Research has shown that sodium lauryl sulfate (SLS), a common ingredient in medications, can affect the absorption of fexofenadine. Studies have found that SLS can enhance drug dissolution, potentially improving absorption by the body. In this trial, participants will receive fexofenadine with varying levels of SLS to determine its impact on the drug's entry into the bloodstream. Some evidence suggests that ingredients like SLS can alter drug absorption, possibly leading to more consistent or effective results. However, clear data on how different SLS amounts, such as 3 mg versus 30 mg, affect fexofenadine absorption is lacking. This trial aims to determine if varying SLS levels significantly change the drug's absorption. ^{3 5 6 7 8}

Who Is on the Research Team?

Katherine Yang, PharmD, MPH

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Healthy adults aged 18-64, willing to avoid certain fruit juices and supplements, can join this trial. They must not be extremely obese, allergic to the drug or its components, have low hemoglobin levels, be pregnant/breastfeeding without birth control use, or have liver/kidney/heart diseases.

Inclusion Criteria

Subjects who are willing to avoid ingestion of fruit juices and citrus bioflavonoids, such as grapefruit extract, hesperidin supplement and naringin supplement, for a period extending from one week prior to the initiation of the study until its completion

Written informed consent obtained from the subject and ability for subject to comply with the requirements of the study

Healthy volunteers of all ethnic groups and races

Exclusion Criteria

I have had gastrointestinal issues or surgery.

Subjects with a condition, disease, or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data

Participating in another research study while participating in this research study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive fexofenadine with or without sodium lauryl sulfate in a 3-period crossover design

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Excipient Effect on Drug Absorption
• Sodium Lauryl Sulfate

Trial Overview The study is testing how a common non-drug ingredient called sodium lauryl sulfate (SLS) affects the absorption of Fexofenadine Hydrochloride. Participants will take the drug with varying amounts of SLS to see if there's any difference in how well their body absorbs it.

How Is the Trial Designed?

Group I: Fexofenadine without SLS Experimental Treatment 1 Intervention

Participants will be administered by mouth with a capsule containing 120 mg fexofenadine hydrochloride and 101 mg microcrystalline cellulose

Group II: Fexofenadine and 30 mg SLS Experimental Treatment 1 Intervention

Participants will be administered by mouth with a capsule containing 120 mg fexofenadine hydrochloride, 30 mg SLS and 101 mg microcrystalline cellulose

Group III: Fexofenadine and 3 mg SLS Experimental Treatment 1 Intervention

Participants will be administered by mouth with a capsule containing 120 mg fexofenadine hydrochloride, 3 mg SLS and 101 mg microcrystalline cellulose

Excipient Effect on Drug Absorption is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Sodium lauryl sulfate for:

• Approved as an excipient in various medicinal products

Approved in United States as Sodium lauryl sulfate for:

• Approved as an inactive ingredient in various drug products

Approved in Canada as Sodium lauryl sulfate for:

• Approved as a non-medicinal ingredient in various drug products

Approved in Japan as Sodium lauryl sulfate for:

• Approved as an excipient in various medicinal products

Approved in China as Sodium lauryl sulfate for:

• Approved as an excipient in various medicinal products

Approved in Switzerland as Sodium lauryl sulfate for:

• Approved as an excipient in various medicinal products

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

Published Research Related to This Trial

Sodium lauryl sulfate significantly enhances the absorption of the antibiotic cefadroxil in the colon, with absorption rates increasing up to 7-fold at higher surfactant concentrations, indicating a strong interaction with the intestinal membrane.

The study suggests that the mechanism behind this increased absorption is related to the surfactant's effect on membrane polarity and its adsorption to the intestinal absorbent membrane, rather than micelle solubilization of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental studies on the influence of surfactants on intestinal absorption of drugs. Cefadroxil as model drug and sodium lauryl sulfate as model surfactant: studies in rat colon. Sancho-Chust, V., Fabra-Campos, S., Gómez-Meseguer, V., et al.[2013]

Excipients can significantly influence drug absorption, and the Biopharmaceutics Classification System (BCS) has specific guidelines on how much these excipients can change for drugs to qualify for a biowaiver, particularly for BCS Class 1 and 3 compounds.

For BCS Class 1 drugs, changes in excipients are unlikely to affect absorption, while for Class 3 drugs, only a few mechanisms are identified that could impact absorption, suggesting that careful selection and understanding of excipients can help ensure drug efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential for pharmaceutical excipients to impact absorption: A mechanistic review for BCS Class 1 and 3 drugs. Flanagan, T.[2019]

Excipient concentrations in the gastrointestinal tract can significantly affect the absorption of poorly water-soluble and poorly permeable drugs, highlighting the importance of formulation in oral drug delivery.

The study suggests that factors like dose volume and excipient dose should be considered when estimating drug absorption in humans, and emphasizes the need for more research on excipient concentrations in luminal fluids to better understand their impact on drug efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Dose Volume and Excipient Dose on Luminal Concentration and Oral Drug Absorption. Aungst, BJ.[2021]

Surfactants used in oral pharmaceutical products can reduce the viability of intestinal epithelial cells and disrupt barrier integrity, raising concerns about their safety based on in vitro and animal studies.

Some commonly used emulsifiers in oral products may be linked to serious health issues like ulcerative colitis and certain metabolic disorders, indicating a need for careful evaluation of their safety in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of surfactant excipients in oral drug formulations. Maher, S., Geoghegan, C., Brayden, DJ.[2023]

Excipients, even in small amounts, can significantly impact the bioavailability of drugs like risperidone and alendronate, challenging existing regulatory guidelines from the US-FDA and WHO regarding their effects.

The study highlights that waivers for in vivo bioequivalence studies should be approached with caution, as variations in excipient composition can lead to substantial differences in drug absorption, even when amounts are considered 'normal' by regulatory standards.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactions between active pharmaceutical ingredients and excipients affecting bioavailability: impact on bioequivalence. García-Arieta, A.[2014]

Sodium lauryl sulfate (SLS), commonly used to enhance drug dissolution, unexpectedly worsened the dissolution of ritonavir (RTV) in acidic conditions due to the formation of a poorly soluble salt, [RTV2+][LS-]2.

The study found that when SLS concentration is low, it can lead to precipitation of this salt, negatively impacting the bioavailability of RTV, highlighting the need for caution when formulating basic drugs with SLS in acidic environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanism for the Reduced Dissolution of Ritonavir Tablets by Sodium Lauryl Sulfate. Guo, Y., Wang, C., Dun, J., et al.[2020]

Pharmaceutical excipients, which are often thought to be inactive, can actually influence the absorption and metabolism of drugs by interacting with metabolic enzymes and transporters in the gastrointestinal tract.

Variations in excipients between drug formulations can lead to bio-inequivalence, potentially affecting clinical outcomes, especially for drugs classified under the Biopharmaceutics Classification System (BCS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Pharmaceutical Excipients on Gastrointestinal Tract Metabolic Enzymes and Transporters-an Update. Zhang, W., Li, Y., Zou, P., et al.[2018]

Dioctyl sodium sulfosuccinate significantly enhances the gastrointestinal absorption of phenolsulfonphthalein in rats, with maximum effectiveness observed at its ED50 concentration, likely due to increased intestinal membrane permeability.

In contrast, poloxalene does not enhance drug absorption and can actually decrease it at higher concentrations due to micellar entrapment of the drug, demonstrating that not all surfactants have the same effect on drug absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of surfactants on absorption through membranes III: effects of dioctyl sodium sulfosuccinate and poloxalene on absorption of a poorly absorbable drug, phenolsulfonphthalein, in rats. Malik, SN., Canaham, DH., Gouda, MW.[2019]

A successful tablet formulation was developed for a poorly water-soluble immunosuppressive drug using sodium lauryl sulfate (SDS), achieving good mechanical properties and chemical stability despite challenges with the drug's compressibility and stability.

The drug release rate from the tablet was primarily influenced by the particle size of the drug and was governed by surface erosion of the tablet matrix, indicating that formulation strategies can effectively enhance drug solubility and release.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and characterization of a surfactant-enriched tablet formulation for oral delivery of a poorly water-soluble immunosuppressive agent. Ruddy, SB., Matuszewska, BK., Grim, YA., et al.[2019]

Sodium lauryl sulfate (SLS) acts as a nonspecific inhibitor of the carrier-mediated absorption of cefadroxil, leading to a significant reduction in its absorption capacity at lower concentrations of the antibiotic (0.1 mg/ml).

At higher concentrations of cefadroxil (10.0 mg/ml), SLS enhances the passive absorption of the antibiotic, resulting in improved absorption rates, indicating that the effect of SLS on cefadroxil absorption is concentration-dependent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental studies on the influence of surfactants on intestinal absorption of drugs. Cefadroxil as model drug and sodium lauryl sulfate as model surfactant: studies in rat duodenum. Sancho-Chust, V., Bengochea, M., Fabra-Campos, S., et al.[2013]

Sodium lauryl sulfate (SLS) significantly enhances the penetration of certain compounds like tritiated water and nickel through human cadaver skin, with a clear dose-effect relationship observed at concentrations of 0.25%, 2%, and 10%.

However, SLS does not affect the penetration of hydrocortisone, indicating that its effects are selective based on the physicochemical properties of the compounds tested.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of sodium lauryl sulfate (SLS) on in vitro percutaneous penetration of water, hydrocortisone and nickel. Frankild, S., Andersen, KE., Nielsen, GD.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04534153

Excipient Effect on Drug Absorption in Humans The purpose of this study is to determine if sodium lauryl sulfate (SLS), a non-drug ingredient commonly added in drug products, affect absorption of drugs ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04534153

Excipient Effect on Drug Absorption in Humans The purpose of this study is to determine if sodium lauryl sulfate (SLS), a non-drug ingredient commonly added in drug products, affect absorption of drugs.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3160949/

Improvement of effect of water-in-oil microemulsion as an ... Overall, the results indicate that the microemulsion was effective for enhancing the oral absorption of fexofenadine, and fexofenadine- loaded microemulsion ...

4. jpharmsci.org jpharmsci.org/article/S0022-3549(24)00225-9/pdf

Fexofenadine The results of experimental solubility values are presented in. Table 2. The solubility values exhibited a similar trend to those reported in ...

5. ajptonline.com ajptonline.com/HTMLPaper.aspx?Journal=Asian%20Journal%20of%20Pharmacy%20and%20Technology;PID=2022-12-4-2

Design, Formulation and Evaluation of Fexofenadine HCl ... The therapeutic effectiveness of a drug product intended for oral administration depends on its gastrointestinal absorption. Dissolution is often the rate ...

6. sigmaaldrich.com sigmaaldrich.com/sds/sial/436143?srsltid=AfmBOoqAoEvEhF3tGyThUNP3vPB1LY6gybOTbIc255L1k7bZodnvUuSB

SAFETY DATA SHEET RTECS: WT1050000 sneezing, The sodium salt of dodecyl sulfate has been reported to cause pulmonary sensitization resulting in hyperactive airway ...

7. sigmaaldrich.com sigmaaldrich.com/sds/sial/l4509?srsltid=AfmBOopCOzXx0scd7mwnJzwUOHMaTDATLyR_yhm2hSHQUhOWe8ExcrFy

SAFETY DATA SHEET RTECS: WT1050000 sneezing, The sodium salt of dodecyl sulfate has been reported to cause pulmonary sensitization resulting in hyperactive airway ...

8. fishersci.com fishersci.com/store/msds?partNumber=S5293&productDescription=SOD+LAURYL+SULFATE+NF%2FFCC+3KG&vendorId=VN00033897&countryCode=US&language=en

SAFETY DATA SHEET Precautionary Statements. Prevention. Wash face, hands and any exposed skin thoroughly after handling. Do not eat, drink or smoke when using ...