Research

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21 pages, 1750 KiB

Open AccessArticle

Optimization of the Production Process of Clinical-Grade Human Salivary Gland Organoid-Derived Cell Therapy for the Treatment of Radiation-Induced Xerostomia in Head and Neck Cancer

by Jacoba van Zanten, Annelies Jorritsma-Smit, Hans Westra, Mirjam Baanstra, Anne de Bruin-Jellema, Derk Allersma, Bahez Gareb and Rob P. Coppes

Pharmaceutics 2024, 16(3), 435; https://doi.org/10.3390/pharmaceutics16030435 - 21 Mar 2024

Viewed by 725

Abstract

Head and neck cancer is a common cancer worldwide. Radiotherapy has an essential role in the treatment of head and neck cancers. After irradiation, early effects of reduced saliva flow and hampered water secretion are seen, along with cell loss and a decline [...] Read more.

Head and neck cancer is a common cancer worldwide. Radiotherapy has an essential role in the treatment of head and neck cancers. After irradiation, early effects of reduced saliva flow and hampered water secretion are seen, along with cell loss and a decline in amylase production. Currently, there is no curative treatment for radiation-induced hyposalivation/xerostomia. This study aimed to develop and optimize a validated manufacturing process for salivary gland organoid cells containing stem/progenitor cells using salivary gland patient biopsies as a starting material. The manufacturing process should comply with GMP requirements to ensure clinical applicability. A laboratory-scale process was further developed into a good manufacturing practice (GMP) process. Clinical-grade batches complying with set acceptance and stability criteria were manufactured. The results showed that the manufactured salivary gland-derived cells were able to self-renew, differentiate, and show functionality. This study describes the optimization of an innovative and promising novel cell-based therapy. Full article

(This article belongs to the Special Issue Pharmacy Compounding of Personalized Preparation for Specific Patients: Challenges and Advantages)

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11 pages, 608 KiB

Open AccessArticle

Compatibility of Commonly Used Active Pharmaceutical Ingredients in a Ready-to-Use Oral Suspending Vehicle

by Mercedeh Mansourian, Eli Dijkers, Carolina C. V. Silva and Hudson C. Polonini

Pharmaceutics 2023, 15(10), 2388; https://doi.org/10.3390/pharmaceutics15102388 - 26 Sep 2023

Viewed by 1186

Abstract

The present study aimed to evaluate the stability of active pharmaceutical ingredients (APIs) from different pharmacological classes in a compounded oral suspending vehicle. Oral suspensions of amoxicillin trihydrate (50 mg/mL), clozapine (25 mg/mL), indomethacin (5.0 mg/mL), levodopa/carbidopa (10.0/2.5 mg/mL), levothyroxine sodium (T4, 25 [...] Read more.

The present study aimed to evaluate the stability of active pharmaceutical ingredients (APIs) from different pharmacological classes in a compounded oral suspending vehicle. Oral suspensions of amoxicillin trihydrate (50 mg/mL), clozapine (25 mg/mL), indomethacin (5.0 mg/mL), levodopa/carbidopa (10.0/2.5 mg/mL), levothyroxine sodium (T4, 25 µg/mL), lomustine (4.0 and 10.0 mg/mL), methyldopa (25 mg/mL) and procarbazine (10.0 mg/mL) were formulated in SyrSpend^® SF PH4 and the stability was monitored for up to 90 days, except for amoxicillin trihydrate, which was evaluated for 30 days only. The APIs’ stability was determined by measuring percent recovery using stability-indicating high-performance liquid chromatography (HPLC or UHPLC) or titration (amoxicillin trihydrate only). The stability of amoxicillin trihydrate, clozapine, indomethacin and levodopa/carbidopa were studied at both refrigerated (2–8 °C) and room temperature (20–25 °C). Lomustine, procarbazine, and methyldopa were studied at refrigerated temperature only. Our data demonstrated promising stability for the compounded suspensions containing various APIs, investigated in SyrSpend^® SF PH4, as all APIs exhibited stability throughout the study duration and met content uniformity criteria. These findings lead to the conclusion that the tested compounded oral suspensions present a viable approach for creating personalized, age-appropriate formulations. The capacity to ensure dose consistency and stability using APIs from diverse pharmacological classes renders them suitable choices for both pediatric and geriatric patients. Full article

(This article belongs to the Special Issue Pharmacy Compounding of Personalized Preparation for Specific Patients: Challenges and Advantages)

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11 pages, 409 KiB

Open AccessArticle

Product Validation and Stability Testing of Pharmacy Compounded Cholic Acid Capsules for Dutch Patients with Rare Bile Acid Synthesis Defects

by Yasmin Polak, Bart A. W. Jacobs, Natalja Bouwhuis, Carla E. M. Hollak, Maurice A. G. M. Kroon and Elles Marleen Kemper

Pharmaceutics 2023, 15(3), 773; https://doi.org/10.3390/pharmaceutics15030773 - 26 Feb 2023

Viewed by 1404

Abstract

Bile acid synthesis defects (BASDs) comprise a group of rare diseases that can be severely disabling. Bile acid supplementation with 5 to 15 mg/kg cholic acid (CA) has been hypothesized to decrease endogenous bile acid production, stimulate bile secretion, and improve bile flow [...] Read more.

Bile acid synthesis defects (BASDs) comprise a group of rare diseases that can be severely disabling. Bile acid supplementation with 5 to 15 mg/kg cholic acid (CA) has been hypothesized to decrease endogenous bile acid production, stimulate bile secretion, and improve bile flow and micellar solubilization, thereby improving the biochemical profile and potentially slowing down disease progression. Currently, CA treatment is unavailable in the Netherlands, and CA capsules were compounded by the Amsterdam UMC Pharmacy from CA raw material. This study aims to determine the pharmaceutical quality and stability of the pharmacy compounded CA capsules. Pharmaceutical quality tests were performed on 25 mg and 250 mg CA capsules according to general monographs of the European Pharmacopoeia 10th ed. For the stability study, the capsules were stored under long-term conditions (25 °C ± 2 °C/60% ± 5% RH) and accelerated conditions (40 °C ± 2 °C/75% ± 5% RH). Samples were analyzed at 0, 3, 6, 9 and 12 months. The findings demonstrate that the pharmacy compounded CA capsules within a range of 25–250 mg that complied with the European regulations in regard to product quality and safety. The pharmacy compounded CA capsules are suitable for use in patients with BASD, as clinically indicated. With its simple formulation, pharmacies are provided a guidance on product validation and stability testing when commercial CA capsules are unavailable. Full article

(This article belongs to the Special Issue Pharmacy Compounding of Personalized Preparation for Specific Patients: Challenges and Advantages)

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20 pages, 1601 KiB

Open AccessArticle

Compounding of Liquid and Solid Dose Adjustable Formulations with Pantoprazole: Comparison of Stability, Applicability and Suitability

by Nemanja Todorović, Jelena Čanji Panić, Mina Zavišić, Jelena Krtolica, Radomir Ratajac, Jelena Petrović, Dušica Bosiljčić, Nebojša Kladar, Nataša Milošević and Mladena Lalić-Popović

Pharmaceutics 2023, 15(3), 717; https://doi.org/10.3390/pharmaceutics15030717 - 21 Feb 2023

Cited by 1 | Viewed by 2133

Abstract

Pantoprazole is a model substance that requires dosage form adjustments to meet the needs of all patients. Pediatric pantoprazole formulations in Serbia are mostly compounded as capsules (divided powders), while in Western Europe liquid formulations are more common. The aim of this work [...] Read more.

Pantoprazole is a model substance that requires dosage form adjustments to meet the needs of all patients. Pediatric pantoprazole formulations in Serbia are mostly compounded as capsules (divided powders), while in Western Europe liquid formulations are more common. The aim of this work was to examine and compare the characteristics of compounded liquid and solid dosage forms of pantoprazole. Three syrup bases were used: a sugar-free vehicle for oral solution (according to USP43-NF38), a vehicle with glucose and hydroxypropyl cellulose (according to the DAC/NRF2018) and a commercially available SyrSpend Alka base. Lactose monohydrate, microcrystalline cellulose and a commercially available capsule filler (excipient II, composition: pregelatinized corn starch, magnesium stearate, micronized silicon dioxide, micronized talc) were used as diluents in the capsule formulations. Pantoprazole concentration was determined by the usage of the HPLC method. Pharmaceutical technological procedures and microbiological stability measurements were performed according to the recommendations of the EP10. Although dose appropriate compounding with pantoprazole is suitable using both liquid vehicles as well as solid formulations, chemical stability is enhanced in solid formulation. Nevertheless, according to our results, if liquid formulation is a pH adjusted syrup, it could be safely kept in a refrigerator for up to 4 weeks. Additionally, liquid formulations could be readily applied, while solid formulation should be mixed with appropriate vehicles with higher pH values. Full article

(This article belongs to the Special Issue Pharmacy Compounding of Personalized Preparation for Specific Patients: Challenges and Advantages)

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19 pages, 1473 KiB

Open AccessArticle

Development of an Oral Liquid Formulation of Nicardipine Hydrochloride Compounded with Simple Excipients for the Treatment of Pediatric Hypertension

by Marine Cavelier, Henri Gondé, Damien Costa, Fabien Lamoureux, Tony Pereira, Nimrod Buchbinder, Rémi Varin and Charles Hervouët

Pharmaceutics 2023, 15(2), 446; https://doi.org/10.3390/pharmaceutics15020446 - 29 Jan 2023

Cited by 1 | Viewed by 2542

Abstract

Nicardipine hydrochloride is an anti-hypertensive drug that is used off-label to treat hypertension in children. A previous oral formulation of nicardipine hydrochloride was developed using a commercial vehicle as an excipient. However, ready-to-use vehicles are prone to supply shortages, and their composition may [...] Read more.

Nicardipine hydrochloride is an anti-hypertensive drug that is used off-label to treat hypertension in children. A previous oral formulation of nicardipine hydrochloride was developed using a commercial vehicle as an excipient. However, ready-to-use vehicles are prone to supply shortages, and their composition may undergo substantial modifications. The aim of this study was to propose a new oral formulation of nicardipine hydrochloride 2 mg/mL using simple excipients. The formulation included hydroxypropylmethylcellulose, simple syrup, polysorbate 80, sodium saccharin, citrate buffer, strawberry flavor and 0.2% potassium sorbate. The uniformity of content was maintained before and after agitation. Nicardipine hydrochloride concentration assessed by HPLC-MS/MS remained above 90% for 365 days before opening and for 28 days after opening. pH and osmolality were maintained throughout the study, and no microbial contamination was observed. The uniformity of mass of the delivered doses was evaluated using four different devices. A new oral formulation of nicardipine hydrochloride 2 mg/mL was developed using simple and safe excipients. Pharmacological and clinical parameters remain to be assessed and compared with those of the previous formulation. Full article

(This article belongs to the Special Issue Pharmacy Compounding of Personalized Preparation for Specific Patients: Challenges and Advantages)

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17 pages, 2415 KiB

Open AccessArticle

Extemporaneous Preparation of 20 mg/mL Ganciclovir in Artificial Tears in Comparison with Sterile Water for Ophthalmic Administration: Formulation and Stability Study

by Jiraporn Leanpolchareanchai, Patamaporn Tangteerakoon, Patcharin Supapsophon, Somsiri Sukavatcharin, Pornchai Simaroj and Jiraphong Suksiriworapong

Pharmaceutics 2023, 15(1), 208; https://doi.org/10.3390/pharmaceutics15010208 - 06 Jan 2023

Viewed by 2420

Abstract

Ganciclovir is available as a lyophilized powder for reconstitution and is normally used to treat ophthalmic viral infections. The use of ganciclovir in artificial tears containing hydrocolloid polymers may prove beneficial to patients during drug application, by prolonging contact time and providing a [...] Read more.

Ganciclovir is available as a lyophilized powder for reconstitution and is normally used to treat ophthalmic viral infections. The use of ganciclovir in artificial tears containing hydrocolloid polymers may prove beneficial to patients during drug application, by prolonging contact time and providing a moistening effect. Therefore, this study aimed to extemporaneously prepare 20 mg/mL ganciclovir in artificial tears and compare its stability with that of a similar concentration of ganciclovir in sterile water (SWI) for ophthalmic administration. First, a compatibility study of the drug with commercial artificial tears found that it was compatible with artificial tears containing sodium hyaluronate (HYA). Subsequently, ganciclovir/0.1% HYA (HYA0.1) and ganciclovir/SWI eyedrops (EDs) in low-density polyethylene (LDPE) eyedrop bottles packed in light-shielded zipper bags were evaluated for their stability at 5 ± 3 °C and 30 ± 2 °C. The results revealed that ganciclovir/SWI ED had good physicochemical and microbiological stability when stored at 5 ± 3 °C for 12 weeks and at 30 ± 2 °C for 8 weeks. Meanwhile, ganciclovir/HYA0.1 ED was stable for 8 weeks when kept at 5 ± 3 °C and at 30 ± 2 °C, but ganciclovir in 0.3% HYA ED could be stored at 5 ± 3 °C for 8 weeks. Nevertheless, particulate matter may need to be investigated using a suitable method to ensure the absence of invisible particles in these preparations. Of these results, ganciclovir/HYA artificial tears and SWI EDs show potential for use as home medications for the treatment of ophthalmic viral infections. Full article

(This article belongs to the Special Issue Pharmacy Compounding of Personalized Preparation for Specific Patients: Challenges and Advantages)

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Review

Jump to: Research

13 pages, 296 KiB

Open AccessReview

Prevalence, Risk, and Challenges of Extemporaneous Preparation for Pediatric Patients in Developing Nations: A Review

by Sri Hartati Yuliani, Dina Christin Ayuning Putri, Dita Maria Virginia, Michael Raharja Gani and Florentinus Dika Octa Riswanto

Pharmaceutics 2023, 15(3), 840; https://doi.org/10.3390/pharmaceutics15030840 - 04 Mar 2023

Cited by 8 | Viewed by 3384

Abstract

Extemporaneous preparations are still widely prescribed for pediatric patients with special treatments of certain doses and/or combinations of drugs. Several problems related to extemporaneous preparations have been linked to the incidence of adverse events or a lack of therapeutic effectiveness. Developing nations are [...] Read more.

Extemporaneous preparations are still widely prescribed for pediatric patients with special treatments of certain doses and/or combinations of drugs. Several problems related to extemporaneous preparations have been linked to the incidence of adverse events or a lack of therapeutic effectiveness. Developing nations are facing the challenges of compounding practices. The prevalence of compounded medication in developing nations must be explored to determine the urgency of compounding practices. Furthermore, the risks and challenges are described and explained through investigation and collection of numerous scientific articles from reputable databases, including Web of Science, Scopus, and PubMed. Pediatric patients need compounded medication related to the appropriate dosage form and dosage adjustment. Notably, it is important to observe extemporaneous preparations in order to provide patient-oriented medication. Full article

(This article belongs to the Special Issue Pharmacy Compounding of Personalized Preparation for Specific Patients: Challenges and Advantages)

16 pages, 770 KiB

Open AccessReview

An Adequate Pharmaceutical Quality System for Personalized Preparation

by Marta Uriel, Diego Marro and Carlota Gómez Rincón

Pharmaceutics 2023, 15(3), 800; https://doi.org/10.3390/pharmaceutics15030800 - 01 Mar 2023

Cited by 1 | Viewed by 1691

Abstract

The pharmacy compounding of personalized preparations has evolved a great deal, and with it, the way of working and the legal requirements have also evolved. An adequate pharmaceutical quality system for personalized preparations presents fundamental differences with respect to the system designed for [...] Read more.

The pharmacy compounding of personalized preparations has evolved a great deal, and with it, the way of working and the legal requirements have also evolved. An adequate pharmaceutical quality system for personalized preparations presents fundamental differences with respect to the system designed for industrial medicines since the size, complexity, and characteristics of the activity of the manufacturing laboratory and the applications and uses of the manufactured medicines must be taken into account. Legislation must advance and adapt to the needs of personalized preparations, filling the deficiencies currently found in this field. The limitations of personalized preparation in its pharmaceutical quality system are analysed and a method based on a proficiency testing program specially designed to overcome these limitations is proposed: the Personalized Preparation Quality Assurance Program (PACMI). This method makes it possible to expand the samples and destructive tests, and dedicate more resources, facilities, and equipment. It allows for more in-depth knowledge of the product and the processes used, and for proposed improvements that increase the overall quality for improved patient health. PACMI introduces tools used in risk management in order to guarantee the quality of an essentially heterogeneous service: personalized preparation. Full article

(This article belongs to the Special Issue Pharmacy Compounding of Personalized Preparation for Specific Patients: Challenges and Advantages)

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