Immediate-release granule formulation of hydrocortisone, Alkindi®, for treatment of paediatric adrenal insufficiency (Infacort development programme)
Abstract
INTRODUCTION: Treatment of paediatric patients with adrenal insufficiency is challenging due to the lack of appropriate glucocorticoid preparations for children, and the use of either pharmacy- or parent-compounded hydrocortisone tablets. Alkindi (hydrocortisone granules in capsules for opening) is a new therapeutic option for paediatric adrenal insufficiency. Areas Covered: Drawbacks of current therapy and formulation and clinical trial programme for Alkindi. Expert Commentary: Compounding hydrocortisone has multiple issues including inconsistent dosing with under and over treatment and practical problems for parents who compound the drug themselves or travel long distances to a compounding pharmacy and the cost of compounding by the pharmacy. Alkindi® is a novel paediatric formulation of immediate release hydrocortisone licensed for use in paediatric adrenal insufficiency. Alkindi® is formulated to address the needs of neonates, infants and young children, being available at appropriate paediatric doses of 0.5, 1.0, 2.0 and 5.0 mg, is multiparticulate, allowing either direct oral dosing or dosing mixed with food, is taste masked to obscure the bitter taste of hydrocortisone and is bioequivalent to current hydrocortisone preparations. Clinical trials in young children with adrenal insufficiency demonstrated cortisol levels after dosing similar to those seen in healthy children and the drug was well tolerated and favoured over current therapy by parents. Alkindi® will provide a licenced treatment option for accurate dosing in children with adrenal insufficiency where compounded adult tablets of hydrocortisone are unsuitable.
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Written from the paper’s full text.
TL;DR
Alkindi® is an immediate-release, taste-masked hydrocortisone granule formulation developed for paediatric adrenal insufficiency and licensed in the EU via a paediatric use marketing authorisation. The development programme reported bioequivalence to immediate-release hydrocortisone in adults and rapid cortisol absorption with good palatability and tolerability in children from neonates to 6 years.
Key findings
- In a phase 1 study in 16 dexamethasone-suppressed healthy adult male volunteers, Alkindi® was bioequivalent to reference immediate-release hydrocortisone tablets at a 10 mg dose; dose proportionality was also evaluated at 0.5, 2.0, 5.0 and 10 mg.
- In the phase 3 Infacort 003 study, 24 children with adrenal insufficiency were studied in sequential age cohorts: 12 aged 2–6 years, 6 aged 1 month–2 years, and 6 neonates aged <28 days. 23/24 had congenital adrenal hyperplasia and one had hypopituitarism; median age was 3 years 3 months, 54.2% were male, and all subjects were white.
- All children were successfully dosed with a median dose of 2 mg. Cortisol increased from baseline to Cmax at 60 minutes; overall geometric mean ± SD Cmax was 575.8 ± 299.5 nmol/L (2 years–6 years: 547.1 ± 82.9 nmol/L; 1 month–2 years: 450.1 ± 88.9 nmol/L; <28 days: 815.7 ± 474.9 nmol/L).
- Palatability was favourable: 82.6% of parents agreed/strongly agreed that their child found swallowing Alkindi® easy, and 95.5% said they would prefer Alkindi® over their usual hydrocortisone formulation. No serious adverse events occurred; adverse events were mild, most commonly diarrhoea, vomiting and rash, and were not attributed to investigational product.
- In a safety extension, 18 subjects elected to continue and 12 remained on treatment at the time of writing. Dropouts among older children aged 2–6 years related to dosing/behavioural refusal; after allowing sprinkling of granules on yoghurt or fruit mousse, there were no further dropouts. At one year, patients had good disease control, no abnormal progression in pubertal status, and growth as expected. Alkindi® received EU centralised paediatric use marketing authorisation on 9 February 2018.
Methods
- This is a narrative review/development programme summary of Alkindi® (development name Infacort), developed under the EU-FP7 TAIN project, covering phase 1 and phase 3 clinical studies.
- Phase 1: single-centre, open-label, randomised crossover study in 16 dexamethasone-suppressed healthy adult male volunteers, comparing pharmacokinetics of Alkindi® with reference hydrocortisone tablets at 10 mg and evaluating dose proportionality at 0.5, 2.0, 5.0 and 10 mg.
- Phase 3: sequential age-cohort, single-arm pharmacokinetic study at Charité hospital in Berlin in 24 paediatric patients with adrenal insufficiency. Patients received a morning Alkindi® dose identical to their usual compounded hydrocortisone dose; blood sampling occurred at 0, 60 and 240 minutes. The primary endpoint was maximum serum cortisol concentration up to 240 minutes after administration, measured by liquid chromatography-mass spectrometry; secondary endpoints included palatability via newly developed 5-point Likert questionnaires, adverse events and vital signs.
Limitations
- The paper does not state formal limitations.
- Evident from the text: the phase 3 study was single-arm, small (n=24), had no comparator, used short blood sampling at 0, 60 and 240 minutes, was conducted at a single centre, and enrolled only white subjects, mostly with congenital adrenal hyperplasia, limiting generalisability. The safety extension was also small and ongoing (18 elected to continue; 12 remained at writing). The article is a narrative review/commentary rather than a systematic review.
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Cites
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Claims the paper makes
0 of 21 cited sources checked · 0 supported · 0 flagged
- Findingown data§ Clinical studies with Alkindi®:
95.5% of parents said they would prefer Alkindi for their child's treatment over their usual hydrocortisone formulation.
“95.5% said that they would prefer Alkindi® for their child's treatment over their usual hydrocortisone formulation.”
Quote in the paperNot a substantial claim- Rests on an assumption: The new 5-point Likert palatability questionnaires developed for parents and patients are valid measures of ease of administration and treatment preference.
- Findingown data§ Clinical studies with Alkindi®:
82.6% of parents agreed or strongly agreed that their child found swallowing Alkindi easy.
“82.6% of parents agreed/strongly agreed that their child found swallowing Alkindi® easy”
Quote in the paperNot a substantial claim- Rests on an assumption: The new 5-point Likert palatability questionnaires developed for parents and patients are valid measures of ease of administration and treatment preference.
- Findingown data§ Clinical studies with Alkindi®:
In all children in the phase 3 study, cortisol increased from baseline to a Cmax at 60 minutes.
“In all children cortisol increased from baseline to a Cmax at 60 minutes (Figure 3).”
Quote in the paperSubstantial claim - Findingcitation§ Clinical studies with Alkindi®:
The phase 1 study demonstrated bioequivalence of Alkindi to immediate-release hydrocortisone.
“The study demonstrated bioequivalence of Alkindi® to immediate release hydrocortisone (Figure 2)(5).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] source
Not checked in the free run.
- Premisecitation§ Background and overview of the market:
Children are unable to swallow tablets designed for adults.
“and are unable to swallow tablets designed for adults (5).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] source
Not checked in the free run.
- Premisecitation§ Background and overview of the market:
Children require hydrocortisone doses much smaller than available tablets, of the order of 1-2 mg three times daily in infants.
“children require much smaller doses (of the order of 1-2mg three times daily in infants)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] source
Not checked in the free run.
- Premisecitation§ Background and overview of the market:
Hydrocortisone is only licensed in 10 mg and 20 mg tablet doses in the European Union.
“hydrocortisone is only licensed in 10 and 20mg tablet doses in the European Union”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] source
Not checked in the free run.
- Interpretationcitation§ Clinical studies with Alkindi®:
The rapid absorption and clearance of cortisol after Alkindi was similar to findings in previous studies of children dosed with immediate-release hydrocortisone.
“The rapid absorption and clearance of cortisol was similar to findings in previous studies of children dosed with immediate release hydrocortisone (24).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] source
Not checked in the free run.
- Interpretationcitation§ Infacort Programme- development of a paediatric appropriate immediate-release granule formulation of hydrocortisone:
Alkindi granules allow swallowing even by neonates.
“and allows for swallowing of granules even by neonates (15).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] Neumann U, Clin Endocrinol (Oxf)
Not checked in the free run.
- Interpretationreasoning§ Conclusions:
Alkindi provides a consistent licensed treatment option for accurate dosing in children with adrenal insufficiency where compounded adult tablets of hydrocortisone are unsuitable.
“Alkindi® provides a consistent licenced treatment option for accurate dosing in children with adrenal insufficiency where compounded adult tablets of hydrocortisone are unsuitable.”
Quote in the paperSubstantial claim - Interpretationcitation§ Five-year view:
Replacing the natural circadian rhythm of cortisol is not addressed by Alkindi.
“However, replacing the natural circadian rhythm of cortisol is not addressed by Alkindi® (28).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] source
Not checked in the free run.
- Interpretationreasoning§ Background and overview of the market:
There is a need for a licensed paediatric appropriate formulation of hydrocortisone.
“Thus, there is a need for a licensed paediatric appropriate formulation of hydrocortisone.”
Quote in the paperNot a substantial claim - Interpretationcitation§ Clinical studies with Alkindi®:
The hydrocortisone Cmax after Alkindi was similar to peak concentrations of cortisol in children with intact hypophyseal-pituitary-adrenal axes.
“The hydrocortisone Cmax was similar to peak concentrations of cortisol in children with intact hypophyseal-pituitary-adrenal axes (25).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] source
Not checked in the free run.
- Rests on an assumption: Similarity of hydrocortisone Cmax after Alkindi in children with adrenal insufficiency to peak cortisol concentrations in children with intact hypophyseal-pituitary-adrenal axes indicates appropriate replacement.
- May combine two claims. 14
- Classified as probably not a substantial claim. 3
May combine two claims.
Findingown data§ Clinical studies with Alkindi®:In the phase 3 study, 23 of 24 children had congenital adrenal hyperplasia and one had hypopituitarism; median age was 3 years 3 months, 54.2% were male and all subjects were white.
“23 of the 24 children studied had Congenital Adrenal Hyperplasia and one patient had hypopituitarism, the median age was 3 years and 3 months, 54.2% were male and all subjects were white.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ Clinical studies with Alkindi®:All children in the phase 3 study were successfully dosed with a median dose of 2 mg.
“All children were successfully dosed with a median dose of 2mg.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ Clinical studies with Alkindi®:At one year, patients on Alkindi had good disease control, no abnormal progression in pubertal status and growth was as expected.
“At one year, patients on Alkindi® had good disease control, no abnormal progression in pubertal status and growth was as expected.”
Quote in the paperSubstantial claim- Rests on an assumption: The one-year safety extension assessments of disease control, pubertal progression and growth reflect good disease control and expected growth.
May combine two claims.
Premisecitation§ Background and overview of the market:Parents find crushing tablets difficult; 27% report not having been instructed in how to prepare doses, and for those that did have instruction, only 10% reported having repeat training.
“Parents find crushing tablets difficult: 27% report not having been instructed in how to prepare doses, and for those that did have instruction, only 10% reported having repeat training.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] Webb EA, 2017, Endocrine Abstracts
Not checked in the free run.
May combine two claims.
Premisecitation§ Background and overview of the market:Excess glucocorticoid replacement in children is associated with poor growth, osteoporosis later in life, obesity, hypertension, depression and increased risk of cardiovascular disease.
“treatment maybe complicated by excess glucocorticoid replacement which puts children at risk of poor growth, osteoporosis later in life, obesity, hypertension, depression and increased risk of cardiovascular disease (3).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3] source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Premisecitation§ Background and overview of the market:Guidance for replacement glucocorticoids in children is to use the lowest possible dose and to use hydrocortisone rather than synthetic steroids such as prednisolone and dexamethasone, which have a greater suppressive effect on growth.
“Guidance for use of replacement glucocorticoids in children is to use the lowest possible dose, and to use the native hormone, hydrocortisone (cortisol), rather than synthetic steroids such as prednisolone and dexamethasone which have a greater suppressive effect on growth (4).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Background and overview of the market:21.4% of pharmacist-compounded hydrocortisone batches failed to meet European pharmacopeia guidelines and a further 3.6% of batches contained no hydrocortisone.
“A recent study, reported that 21.4% of pharmacist-compounded hydrocortisone batches failed to meet European pharmacopeia guidelines and a further 3.6% of batches contained no hydrocortisone (7).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [7] source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Background and overview of the market:In children, the commonest cause of adrenal insufficiency is congenital adrenal hyperplasia.
“in children the commonest cause is Congenital Adrenal Hyperplasia (CAH)(2).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] source
Not checked in the free run.
May combine two claims.
Interpretationown data§ Key issues:Alkindi is an immediate-release hydrocortisone formulation with taste masking, licensed under a PUMA, and provides an easy-to-administer, well-tolerated paediatric formulation which allows accurate dose titration in neonates, infants and children.
“Alkindi®, is an immediate release hydrocortisone formulation with taste masking, licenced under a PUMA, and provides an easy to administer, well tolerated, paediatric formulation which allows accurate dose titration in neonates, infants and children.”
Quote in the paperSubstantial claimMay combine two claims.
Premisecitation§ Infacort Programme- development of a paediatric appropriate immediate-release granule formulation of hydrocortisone:Alkindi is a multiparticulate granule formulation with maximum granule diameter controlled by passing through a 0.8 mm sieve, well below the FDA Guidance sprinkle formulation limit of 2.5 mm diameter.
“Alkindi® is a multiparticulate granule formulation with maximum granule diameter controlled by passing through a 0.8mm sieve i.e. well below the FDA Guidance to industry on sprinkle formulation limits of 2.5mm diameter”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] Neumann U, Clin Endocrinol (Oxf)
Not checked in the free run.
May combine two claims.
Interpretationcitation§ Conclusions:Alkindi is a novel paediatric formulation of immediate-release hydrocortisone licensed for use in paediatric adrenal insufficiency with doses of 0.5, 1.0, 2.0 and 5.0 mg.
“Alkindi® is a novel paediatric formulation of immediate release hydrocortisone licensed for use in paediatric adrenal insufficiency with doses of 0.5, 1.0, 2.0 and 5.0 mg (reference Alkindi SmPC Diurnal Ltd).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Alkindi SmPC Diurnal Ltd
Not checked in the free run.
May combine two claims.
Interpretationreasoning§ Key issues:Currently children with adrenal insufficiency are dependent on compounded hydrocortisone formulations which do not provide accurate dosing, are bitter to taste and are associated with poor disease control resulting in under- and overtreatment, adrenal crises and poor growth.
“Currently children with adrenal insufficiency are dependent on compounded hydrocortisone formulations which do not provide accurate dosing, are bitter to taste and associated with poor disease control resulting in under and over treatment, adrenal crises and poor growth.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ Infacort Programme- development of a paediatric appropriate immediate-release granule formulation of hydrocortisone:Hydrocortisone is rapidly absorbed from the gut with almost 100% bioavailability, reaching peak concentrations around an hour after being taken fasted.
“Hydrocortisone is rapidly absorbed from the gut with almost 100% bioavailability reaching peak concentrations around an hour after being taken fasted (17) .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] Johnson TN, 2017, J Bioequiv Availab
Not checked in the free run.
May combine two claims.
Premisecitation§ Five-year view:A modified-release formulation of hydrocortisone is under development for congenital adrenal hyperplasia by Diurnal Ltd that more closely mimics the overnight physiological pattern of cortisol release and in a phase 2 study improved biochemical control in patients with congenital adrenal hyperplasia.
“A modified release formulation of hydrocortisone is under development for CAH by Diurnal Ltd that more closely mimics the overnight physiological pattern of cortisol release and in a phase 2 study improved biochemical control in patients with CAH (29,30).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [29] Mallappa A, J Clin Endocrinol Metab
Not checked in the free run.
- cites [30] Jones CM, 2017, J Clin Endocrinol Metab
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May combine two claims.
Premisecitation§ Background and overview of the market:Inconsistency in hydrocortisone dose created by compounding can lead to severe clinical consequences with poor disease control due to undertreatment and Cushing's syndrome due to overtreatment.
“The inconsistency in hydrocortisone dose created by compounding can lead to severe clinical consequences with poor disease control due to undertreatment (7) and Cushings syndrome due to overtreatment (11,12).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [7] source
Not checked in the free run.
- cites [11] source
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- cites [12] Hartman MF, Bötcher C, Wudy S, et al. Incorrect dosage of hydrocortisone in individually manufactured capsules by drugstores: a dilemma in the therapy of children with CAH. Hormone Research in Paediatrics. 2010;74:163.
Not checked in the free run.
The paper relies on this without support.
Patients with adrenal insufficiency will die from an adrenal crisis unless cortisol is replaced.
“Patients with adrenal insufficiency will die from an adrenal crisis unless cortisol is replaced”
The paper relies on this without support.
Children with congenital adrenal hyperplasia have excess adrenal androgen secretion due to compensatory pituitary drive, leading to pseudo-precocious puberty and virilisation in both male and female children.
“children with CAH have the additional problem that the compensatory pituitary drive to the adrenal results in excess adrenal androgen secretion leading to pseudo-precocious puberty and virilisation in both male and female children.”
The paper relies on this without support.
The pharmacokinetic profile of Alkindi in dexamethasone-suppressed healthy adult males is predictive of its performance in children with adrenal insufficiency.
“To demonstrate bioequivalence between Alkindi® and the reference hydrocortisone product healthy adult male volunteers were treated with dexamethasone to suppress their hypophyseal-pituitary-adrenal axes.”
The paper relies on this without support.
Similarity of hydrocortisone Cmax after Alkindi in children with adrenal insufficiency to peak cortisol concentrations in children with intact hypophyseal-pituitary-adrenal axes indicates appropriate replacement.
“The hydrocortisone Cmax was similar to peak concentrations of cortisol in children with intact hypophyseal-pituitary-adrenal axes (25).”
The paper relies on this without support.
The new 5-point Likert palatability questionnaires developed for parents and patients are valid measures of ease of administration and treatment preference.
“Secondary endpoints included palatability of Alkindi® (for which new 5 point Likert questionnaires were developed for parents and patients)”
The paper relies on this without support.
The one-year safety extension assessments of disease control, pubertal progression and growth reflect good disease control and expected growth.
“At one year, patients on Alkindi® had good disease control, no abnormal progression in pubertal status and growth was as expected.”
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Minnetti, M., Caiulo, S., Ferrigno, R., Ferroli, B. B., Bottaro, G., Gianfrilli, D., Sbardella, E., Martino, M. C. D., & Savage, M. O. (2019) · Clinical Endocrinology · doi:10.1111/cen.14131 · Cited by 33 · see citing works
A review on taste masked multiparticulate dosage forms for paediatric
AL-Japairai, K. A. S., Almurisi, S. H., Doolaanea, A. A., Mahmood, S., Alheibshy, F., Alobaida, A., Abdul-Halim, N., & Chatterjee, B. (2022) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2022.122571 · Cited by 26 · see citing works
Current and future treatment options for adrenal insufficiency
Arshad, M. F., & Debono, M. (2021) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000637 · Cited by 13 · see citing works
Adrenal crisis in infants and young children with adrenal insufficiency: Management and prevention
Bizzarri, C., Capalbo, D., Wasniewska, M. G., Baronio, F., Grandone, A., & Cappa, M. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1133376 · Cited by 13 · see citing works
“Frontiers in Endocrinology 04 those seen in healthy children and the drug was well tolerated and preferred by several parents over current therapy (21).”
BackgroundRare forms of genetic paediatric adrenal insufficiency: Excluding congenital adrenal hyperplasia
Hasenmajer, V., Ferrigno, R., Minnetti, M., Pellegrini, B., Isidori, A. M., Lenzi, A., Salerno, M., Cappa, M., Chan, L. F., Martino, M. C. D., et al. (2023) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-023-09784-7 · Cited by 13 · see citing works
Kendırcı, H. N. P., Ünal, E., Dündar, İ., Buluş, A. D., Güneş, S. O., & Şıklar, Z. (2024) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.galenos.2024.2024-6-26-s · Cited by 7 · see citing works
“In recent years, 0.5, 1, 2 and 5 mg rapid-release granule formulation preparations of HC (Infacort ® /Alkindi ® , Diurnal Ltd.) have been approved for use in the European Union and the United States (17,18).”
InfluentialStability of Hydrocortisone in Oral Powder Form Compounded for Pediatric Patients in Japan
Saito, J., Yoshikawa, N., Hanawa, T., Ozawa, A., Μatsumoto, T., Harada, T., Iwahashi, K., Nakamura, H., & Yamatani, A. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13081267 · Cited by 6 · see citing works
“5, 1, 2, and 5 mg of hydrocortisone in each capsule [4].”
BackgroundChallenges in managing disorders of sex development associated with adrenal dysfunction
Finkielstain, G. P., & Rey, R. A. (2023) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2023.2256393 · Cited by 5 · see citing works
Steroid Use in the NICU: Treatment and Tapering
McNerney, K. P., & Arbeláez, A. M. (2023) · NeoReviews · doi:10.1542/neo.24-4-e207 · Cited by 4 · see citing works
Linear growth in children and adolescents with congenital adrenal hyperplasia
Savage, M. O. (2024) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000001361 · Cited by 2 · see citing works
Non-Classic Congenital Adrenal Hyperplasia in Childhood: A Review
Bertolucci, G., Tyutyusheva, N., Sepich, M., Baldinotti, F., Caligo, M. A., Sessa, M. R., Peroni, D. G., & Bertelloni, S. (2023) · Sexes · doi:10.3390/sexes4040030 · Cited by 1 · see citing works
Vantaggi delle nuove formulazioni di glucocorticoidi nel trattamento della sindrome adreno-genitale
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“È assorbito rapidamente dal tratto gastrointestinale e aumenta i GC 60 minuti dopo l’assunzione, con livelli ematici di HC e clearance simili al medicinale di riferimento, ma non riproduce il ritmo circadiano [3, 4] (Fig.”
BackgroundAinsworth, S. B. (2020) · doi:10.1093/med/9780198840787.003.0021
Update in Pediatric Endocrinology
Marks, S. D., & Wicklow, B. A. (2023) · Springer eBooks · doi:10.1007/978-3-031-41542-5_14
Kaye, A. D., Khaled, M. E., Bembenick, K. N., Lacey, J., Tandon, A., Kelkar, R. A., Derouen, A. G., Ballaera, C., Chandler, D., Ahmadzadeh, S., et al. (2024) · Cureus · doi:10.7759/cureus.56031
“…positive safety profiles and achieved cortisol levels similar to those in healthy children; furthermore, Alkindi Sprinkle is well tolerated, easy to administer, and can provide accurate doses for different age groups, although it may currently be more expensive than tablet formulations [6,29,21].”
BackgroundInfluentialDisorders of the Adrenal Gland in Children and Adolescents
Katugampola, H., & Krone, N. P. (2023) · Endocrinology · doi:10.1007/978-3-030-18901-3_4-1
Disorders of the Adrenal Gland in Children and Adolescents
Katugampola, H., & Krone, N. P. (2024) · Endocrinology · doi:10.1007/978-3-030-23709-7_4
Congenital Adrenal Hyperplasia
Witchel, S. F., Oberfield, S. E., Fisher, A. S., & Trapp, C. M. (2024) · Springer eBooks · doi:10.1007/978-3-031-66296-6_11
Saito, J., Yamatani, A., Nakamura, H., et al. (2026) · Therapeutic Innovation & Regulatory Science · doi:10.1007/s43441-026-00985-1
“As a new method for dispensing granules to patients, sprinkle capsules—filled with granules or pellet-shaped medications (often mixed into semi-solid foods or suspended in water for ingestion)—have been developed as a pediatric dosage form [ 16 , 17].”
- Authors
- Porter, J., Withe, M., & Ross, R. J.
- Affiliations
- Diurnal (United Kingdom) (GB)
- University of Sheffield (GB)
- Corresponding author
- Ross, Richard J.
- Venue
- Expert Review of Endocrinology & Metabolism
- Publisher
- Informa UK Limited
- Published
- 2018-03-26
- Volume
- 13
- Issue
- 3
- Pages
- 119-124
- ISSN
- 1744-6651 (ISSN-L)
- 1744-8417
- OpenAlex
- W2793724863
- Semantic Scholar
- 65317144d253a2a307cc376beb4fcfbe19f6823d
- Cited by
- 26
- References
- 24
- Citations by year
- 2026: 1 · 2024: 6 · 2023: 7 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 4
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Review of Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Funders
- European Commission under the Framework 7 Programme (HEALTH-F5-2011-281654 -TAIN)
- Diurnal Ltd
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- cortisol, multiparticulate formulation, taste masking, bioequivalence, glucocorticoid dosing
- MeSH terms
- Adolescent, Adrenal Insufficiency, Child, Child, Preschool, Drug Compounding, Humans, Hydrocortisone, Infant, Tablets
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