Product development and quality of pharmacy compounded chenodeoxycholic acid capsules for Dutch cerebrotendinous xanthomatosis patients
Introduction: In 2017 the drug chenodeoxycholic acid (CDCA) became unavailable to Dutch patients with the rare inborn error of metabolism cerebrotendinous xanthomatosis (CTX). This was a direct result of a steep price increase after CDCA was authorized in the EU as an orphan drug. As a result, Dutch...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1264997/full |
| _version_ | 1797658460411658240 |
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| author | Natalja Bouwhuis Natalja Bouwhuis Bart A. W. Jacobs Bart A. W. Jacobs E. Marleen Kemper |
| author_facet | Natalja Bouwhuis Natalja Bouwhuis Bart A. W. Jacobs Bart A. W. Jacobs E. Marleen Kemper |
| author_sort | Natalja Bouwhuis |
| collection | DOAJ |
| description | Introduction: In 2017 the drug chenodeoxycholic acid (CDCA) became unavailable to Dutch patients with the rare inborn error of metabolism cerebrotendinous xanthomatosis (CTX). This was a direct result of a steep price increase after CDCA was authorized in the EU as an orphan drug. As a result, Dutch health insurance companies were unable to reimburse this drug and the availability of CDCA to patients with CTX was directly at risk creating an unmet medical need. CTX is characterized by juvenile cataract, tendon xanthomas, infantile-onset diarrhea, psychomotor retardation and progressive cerebellar ataxia. Treatment with CDCA, when initiated before neurological symptoms are present, can prevent the onset of neurological complications.Methods: To assure continuation of patient treatment with a high quality product, the hospital pharmacy of the Amsterdam UMC developed CDCA capsules as a pharmacy preparation. A simple and robust formulation was developed for capsules in a broad dose range of 35–250 mg, ensuring that both pediatric and adult patients can receive an exact dose tailored to their specific needs. Capsules are prepared manually on a small scale for the individual patient. To assure the quality of the product, product validation and stability studies were performed.Results: The results show that the product complies with all specifications based on the requirements of the European Pharmacopoeia. The capsules contain the declared amount of CDCA, no degradation product or other (microbiological) impurities are formed during the production process and the capsules show a quick dissolution profile. Stability studies indicate that it is a stable product and no impurities increase or arise over time. These results show that these pharmacy preparations are of high quality and comply to Good Manufacturing Practice (GMP) requirements.Discussion: Through our research, we have demonstrated that pharmacy compounding can be a viable alternative in situations where immediate access to essential medication is crucial or when certain drugs are temporarily inaccessible. The purpose of this paper is to offer comprehensive guidance to other pharmacies to improve the availability of currently inaccessible drugs through the practice of pharmacy compounding, thereby facilitating improved patient care. |
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| format | Article |
| id | doaj.art-c87d38a1515441fcae5655a9038314b3 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-11T18:00:24Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-c87d38a1515441fcae5655a9038314b32023-10-17T09:35:05ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-10-011410.3389/fphar.2023.12649971264997Product development and quality of pharmacy compounded chenodeoxycholic acid capsules for Dutch cerebrotendinous xanthomatosis patientsNatalja Bouwhuis0Natalja Bouwhuis1Bart A. W. Jacobs2Bart A. W. Jacobs3E. Marleen Kemper4Department of Pharmacy and Clinical Pharmacology, Amsterdam UMC, Amsterdam, NetherlandsPlatform Medicine for Society, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Pharmacy and Clinical Pharmacology, Amsterdam UMC, Amsterdam, NetherlandsPlatform Medicine for Society, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Experimental Vascular Medicine, Amsterdam UMC, Amsterdam, NetherlandsIntroduction: In 2017 the drug chenodeoxycholic acid (CDCA) became unavailable to Dutch patients with the rare inborn error of metabolism cerebrotendinous xanthomatosis (CTX). This was a direct result of a steep price increase after CDCA was authorized in the EU as an orphan drug. As a result, Dutch health insurance companies were unable to reimburse this drug and the availability of CDCA to patients with CTX was directly at risk creating an unmet medical need. CTX is characterized by juvenile cataract, tendon xanthomas, infantile-onset diarrhea, psychomotor retardation and progressive cerebellar ataxia. Treatment with CDCA, when initiated before neurological symptoms are present, can prevent the onset of neurological complications.Methods: To assure continuation of patient treatment with a high quality product, the hospital pharmacy of the Amsterdam UMC developed CDCA capsules as a pharmacy preparation. A simple and robust formulation was developed for capsules in a broad dose range of 35–250 mg, ensuring that both pediatric and adult patients can receive an exact dose tailored to their specific needs. Capsules are prepared manually on a small scale for the individual patient. To assure the quality of the product, product validation and stability studies were performed.Results: The results show that the product complies with all specifications based on the requirements of the European Pharmacopoeia. The capsules contain the declared amount of CDCA, no degradation product or other (microbiological) impurities are formed during the production process and the capsules show a quick dissolution profile. Stability studies indicate that it is a stable product and no impurities increase or arise over time. These results show that these pharmacy preparations are of high quality and comply to Good Manufacturing Practice (GMP) requirements.Discussion: Through our research, we have demonstrated that pharmacy compounding can be a viable alternative in situations where immediate access to essential medication is crucial or when certain drugs are temporarily inaccessible. The purpose of this paper is to offer comprehensive guidance to other pharmacies to improve the availability of currently inaccessible drugs through the practice of pharmacy compounding, thereby facilitating improved patient care.https://www.frontiersin.org/articles/10.3389/fphar.2023.1264997/fullpharmacy preparationpharmacy compoundingchenodeoxycholic acidcerebrotendinous xanthomatosisproduct validationstability |
| spellingShingle | Natalja Bouwhuis Natalja Bouwhuis Bart A. W. Jacobs Bart A. W. Jacobs E. Marleen Kemper Product development and quality of pharmacy compounded chenodeoxycholic acid capsules for Dutch cerebrotendinous xanthomatosis patients Frontiers in Pharmacology pharmacy preparation pharmacy compounding chenodeoxycholic acid cerebrotendinous xanthomatosis product validation stability |
| title | Product development and quality of pharmacy compounded chenodeoxycholic acid capsules for Dutch cerebrotendinous xanthomatosis patients |
| title_full | Product development and quality of pharmacy compounded chenodeoxycholic acid capsules for Dutch cerebrotendinous xanthomatosis patients |
| title_fullStr | Product development and quality of pharmacy compounded chenodeoxycholic acid capsules for Dutch cerebrotendinous xanthomatosis patients |
| title_full_unstemmed | Product development and quality of pharmacy compounded chenodeoxycholic acid capsules for Dutch cerebrotendinous xanthomatosis patients |
| title_short | Product development and quality of pharmacy compounded chenodeoxycholic acid capsules for Dutch cerebrotendinous xanthomatosis patients |
| title_sort | product development and quality of pharmacy compounded chenodeoxycholic acid capsules for dutch cerebrotendinous xanthomatosis patients |
| topic | pharmacy preparation pharmacy compounding chenodeoxycholic acid cerebrotendinous xanthomatosis product validation stability |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1264997/full |
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