Advancing medication compounding: Use of a pharmaceutical 3D printer to auto-fill minoxidil capsules for dispensing to patients in a community pharmacy

Abstract

Compounding medications in pharmacies is a common practice for patients with prescriptions that are not available commercially, but it is a laborious and error-prone task. The incorporation of emerging technologies to prepare personalised medication, such as 3D printing, has been delayed in smaller pharmacies due to concerns about potential workflow disruptions and learning curves associated with novel technologies. This study examines the use in a community pharmacy of a pharmaceutical 3D printer to auto-fill capsules and blisters using semisolid extrusion, incorporating an integrated quality control system. This retains the customisation and automation advantages of 3D printing, speeding up the manufacturing process while increasing familiarity for pharmacists. Minoxidil capsules (2.5 mg and 5 mg doses) were prepared using a pharmaceutical 3D printer and dispensed to 9 patients in a community compounding pharmacy setting in Spain. This innovative production method was compared to the conventional manual capsule filling. All capsules met the European Pharmacopeia standards for mass uniformity, drug content and dissolution, and demonstrated stability at 25 °C and 65 % relative humidity for three months, matching the typical treatment duration. The 3D printer offers greater precision and efficiency and reduced operator involvement by more than half compared to manual capsule filling, making the process faster and more cost-effective. This study offers for the first time a clear roadmap for implementing a pharmaceutical 3D printer in a community pharmacy for automated compounding to prepare reliable and precise personalised medication for patients, marking a valuable step forward in precision medicine.

Introduction

Most treatments adhere to a standardised approach, prescribing the same medication to different patients without considering their individual needs. This “one-size-fits-all” approach overlooks the impact of relevant patient characteristics (e.g. age, co-morbidities, genetics, metabolism, etc) on the effectiveness of treatments, and frequently results in the appearance of side effects (Litman, 2019, Goetz and Schork, 2018). Therefore, a shift towards personalised therapies with tailored doses or alternative dosage forms is required (Pravin and Sudhir, 2018, Englezos et al., 2023).

The personalisation of treatments for patients with special medical needs and at doses not available commercially is currently done by compounding in pharmacies within hospitals and the community. In this small-scale approach, medicines are prepared manually by combining and mixing different pharmaceutical products (drugs and excipients) in precise amounts, based on a medical prescription (AEMPS, 2023a, FDA, 2024). This approach enables the personalisation of doses (Sinclair, 2018), the preparation of alternative dosage forms, the avoidance of allergens, the adaptation of treatments to paediatric patients (Heitman et al., 2019, Rouaz-El-Hajoui et al., 2024) and addressing the shortage of commercial medicines (Torrado-Salmeron et al., 2022), making compounding an essential element of healthcare systems worldwide.

Compounded formulations represent a small percentage of all prescribed medications, so compounding is normally subject to more relaxed regulations than mass manufactured medication (FDA, 2024, Allen, 2020). The commercialisation of compounded medicines does not require approval from regulatory authorities, such as the Food and Drug Administration (FDA) in the US or the European Medicines Agency (EMA) in Europe, and in most countries, it does not require Good Manufacturing Practices (GMP) (FDA, 2024, Donovan et al., 2018, The European Parliament, 2001, European Commission, 2025). Compounding errors are common and can result in serious side effects or even the death of a patient. In 2012, contaminated steroid injections prepared by a Compounding Centre in the US resulted in 64 reported deaths, due to fungal meningitis (Abbas et al., 2016). Moreover, a FDA report analysing 29 medicinal products from 12 compounding pharmacies concluded that, while the analytical testing failure rate for commercially manufactured medicines was under 2 %, this rate rose to 34 % for compounded formulations, mostly due to potency-related issues (FDA, 2018). More recently, multiple US states have reported quality testing failure rates of 11–53 % for compounded medicines with many listing potencies ranging from 0-450 % from the actual prescription (Gudeman et al., 2013).

Automation technologies such as three dimensional (3D) printing, computer vision and internet of things could improve compounding precision, efficiency and medicines quality (Batson et al., 2020, Yoon et al., 2024, Beer et al., 2023). Among those technologies, pharmaceutical 3D printing (3DP), also known as additive manufacturing, is an innovative manufacturing method allowing personalisation in terms of dose, shape, flavour, colour, release profile and drug combination, all while performing quality control monitoring to guarantee safety (Beer et al., 2023, Jandyal et al., 2022, Awad et al., 2018). 3DP allows to produce medicines automatically and can be coupled with non-destructive quality control technologies. Examples of these quality control technologies or Process Analytical Technologies (PATs) include an inbuilt analytical balance for mass uniformity control, a near-infrared (NIR) or RAMAN spectroscopy sensor for content uniformity and pressure sensors (Bendicho-Lavilla et al., 2024, Díaz-Torres et al., 2022, Jørgensen et al., 2023, Herrada-Manchón et al., 2020, Díaz-Torres et al., 2023). These PATs could ensure a better process performance and produce higher quality medicines (Khairuzzaman et al., 2018).

3DP has been used in multiple clinical studies in hospitals around the world, (Rodríguez-Pombo et al., 2024, Goyanes et al., 2019, Denis et al., 2024) demonstrating its value for treatment compliance in diverse patient populations (paediatrics, geriatrics and patients with dysphagia). However, its widespread use for treating patients has yet to be observed (Seoane-Viaño et al., 2021). Uncertainty surrounding regulatory, ethical and social aspects hinder the implementation of 3D-printed medicines in clinical settings (Seoane-Viaño et al., 2021, Lind et al., 2017). Some reasons include prescribers’ unfamiliarity with the technology, pharmacists’ limited training or expertise in operating 3D printers and an unclear regulatory framework. This extends to aspects such as required equipment, classification of 3D-printed medicines (e.g., tablets, “printlets” (3D-printed tablets), troches, gummies, orodispersible films, etc.), and the implementation of quality standards for point-of-care manufacturing (Herrada-Manchón et al., 2020, Wang et al., 2023, FDA, 2022, MHRA, 2023, Goyanes et al., 2017, Musazzi et al., 2018, Goyanes et al., 2014). An easier alternative for quick implementation in a clinical setting is using a pharmaceutical 3D printer to fill capsules as an automatic material dispenser (Denis et al., 2024). With this approach, the final dosage form is a capsule, even though a 3D printer is used for the filling process. This method allows for automated personalised dosing and quality control while avoiding the unfamiliarity surrounding 3DP.

A drug commonly used in compounding that could benefit from this technology is minoxidil, an active ingredient effective in the treatment of many forms of alopecia (androgenic alopecia, telogen effluvium, chemotherapy, etc.). Although the oral treatment of minoxidil is not commercially authorised in some countries, small batches of hard capsules containing minoxidil at low dose (0.25–5 mg) are commonly prescribed by doctors and compounded in pharmacies as extemporaneous (compounded) formulations (Torrado-Salmeron et al., 2022, Randolph and Tosti, 2021, Watson et al., 2021). Dose accuracy is important to avoid the occurrence of side effects associated with this drug such as facial hypertrichosis, postural hypotension or tachycardia (Suchonwanit et al., 2019).

The aim of this study was to pioneer and demystify the implementation of a pharmaceutical 3D printer as a capsule filling platform for medication production in a community compounding pharmacy. Minoxidil capsules with two different dose strengths (2.5 mg and 5 mg) were prepared through conventional compounding methods and by using a pharmaceutical 3D printer equipped with an in-line quality control system alongside specialised software. In the study, both preparation methods were compared in terms of characteristics of the batches, resources, cost and production time. Additionally, a comprehensive evaluation of the regulatory framework was performed to assess the legal feasibility of using a pharmaceutical 3D printer to manufacture medicines and give them to patients.

Download the full article as PDF here Advancing medication compounding

or read it here

Materials

Minoxidil, polyethylene glycol 4000 (PEG 4000), xanthan gum, size 3 capsules red colour, riboflavin and microcrystalline cellulose (Capsucel®) were purchased from Guinama (Valencia, Spain). Techna 20 SFTM troche base with bitter-bloc technology was obtained from SpecializedRx (Minnesota, US). All materials used are widely utilised in pharmaceutical compounding and were of pharmaceutical grade, suitable for human consumption.

Xela Rodríguez-Maciñeiras, Carlos Bendicho-Lavilla, Carlos Rial, Khalid Garba-Mohammed, Anna Worsley, Eduardo Díaz-Torres, Celia Orive-Martínez, Ángel Orive-Mayor, Abdul W. Basit, Carmen Alvarez-Lorenzo, Alvaro Goyanes,
Advancing medication compounding: Use of a pharmaceutical 3D printer to auto-fill minoxidil capsules for dispensing to patients in a community pharmacy, International Journal of Pharmaceutics, Volume 671, 2025, 125251, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2025.125251.