1. INTRODUCTION
Oral administration is one of the most studied and widely used strategies for systemic drug delivery in many therapeutic areas. It employs a wide range of dosage forms due to its convenience, non-invasive approach, and patient compliance [1]. Many drugs act by maintaining stable, safe, and effective concentrations in the bloodstream for the required duration. Achieving this therapeutic goal requires the careful design of dosage forms that ensure adequate drug release rates and absorption profiles, along with proper medical prescription and patient adherence [2].
Most drugs can be administered through an immediate-release (IR) dosage form without major inconvenience to follow a treatment at prescribed time intervals according to medical instructions. However, due to their chemical nature, some drugs have inherent risks when they are orally administered, whether because of their limited solubility, permeability, instability under physiological conditions, or risk of toxicity due to accumulation in organs and tissues; hence, they are restricted by narrow therapeutic windows. Several decades ago, it was discovered that a strategy to solve this problem was the use of modified drug delivery systems, as they can improve pharmacotherapy by maintaining therapeutic plasma concentrations, reducing dosing frequency, and improving adherence to the pharmacological treatment [3].
Solid oral modified-release dosage forms (SOMRDFs) are classified in two main categories: Delayed-release (DR) and extended-release (ER) [4]. However, the definitions and terminology used for subtypes of SOMRDFs are not consistently standardized among health authorities and researchers worldwide [5,6]. Oral ER formulations can be found in scientific literature and official documents referred to as sustained-release (SR), prolonged-release (PR), controlled-release (CR), timed-release, repeated-release, programmed-release, “long-acting”, “repeat action”, “prolonged-action”, and “ultra-long acting” products. This suggests that different terms may reflect differences in drug release characteristics, or that they are sometimes used arbitrarily, creating ambiguity and hindering a comprehensive understanding of this subject.
Unlike other studies that address the description of specific aspects of modified drug delivery systems, this research focuses on compiling and analyzing information from articles and books in recognized databases, as well as from technical documents issued by the main regulatory authorities across the Americas, regarding terms, concepts, and definitions applicable in these territories for SOMRDFs. As a result, this review clarifies relevant terms and classifications, which can help both the academic and professional health community, as well as non-experts in the health field, to better understand and appropriately apply the terminology related to these health technologies.
2. MATERIALS AND METHODS
2.1. Data sources
This research was conducted using as primary resources original research articles available in the databases ScienceDirect, Springer, PubMed, Taylor & Francis, and Google Scholar.
The literature search was performed using the combinations of the keywords [“Drug modified release (MR)” OR “Drug delivery system” OR “Modified release”] AND “Oral” (quotation marks included), in title and abstract, and restricted to complete scientific articles (excluding conferences, letters, lectures, abstracts, or other type of documents). The last date of search was March 26, 2025.
Scientific review articles and books were used as secondary sources, identified by using the databases and keywords mentioned before. For books, the database Access Pharmacy was also included.
In addition to the research articles and books, official documents from regulatory health authorities in the Americas were also reviewed to identify the definitions and classification of oral MR formulations. These authorities included the Colombian National Food and Drug Surveillance Institute (Instituto Nacional de Vigilancia de Medicamentos y Alimentos, INVIMA); the Peruvian General Directorate of Medicines, Supplies and Drugs (Dirección General de Medicamentos, Insumos y Drogas); the Ecuadorian National Agency for Regulation, Control and Sanitary Surveillance (Agencia Nacional de Regulación, Control y Vigilancia Sanitaria, ARCSA); the Argentinian National Administration of Drugs, Foods and Medical Devices (Administración Nacional de Medicamentos, Alimentos y Tecnología Médica); the Chilean Public Health Institute (Instituto de Salud Pública de Chile); the Paraguayan National Directorate of Sanitary Surveillance (Dirección Nacional de Vigilancia Sanitaria); the Uruguayan Ministry of Public Health—Medicines Division (Ministerio de Salud Pública, División de Medicamentos); the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária, ANVISA); and the U.S. Food and Drug Administration (FDA).
Official national pharmaceutical compendia in the Americas were also consulted, including the Argentinian, Brazilian, Mexican, and United States pharmacopoeias. The official documents were located by targeted searches directly on the official websites of the health authorities, accessed through Google, or directly in the compendia, looking for MR-associated content.
The INVIMA (Colombia) platform was accessed to review the “Unique Medicines Code [Código Único de Medicamentos (CUM)]” report as of June 2025, to compare the pharmaceutical forms assigned by INVIMA with the brand names of each product. For this purpose, the database was filtered in the pharmaceutical-form field using the words “liberación” and “entérica”.
2.2. Studies selection
The reports from scientific databases were selected following the PRISMA flow diagram presented in Figure 1 [7]. The inclusion criteria were:
 | Figure 1. PRISMA flow diagram of the research. [Click here to view] |
– Articles from 2010 to 2024, except those presenting definitions of the different types of oral drug release, for which no time restriction was considered.
– Articles published before 2010 authored by researchers with Hirsch index (H) ≥ 10 [8], verified using Web of Science Journal Citation Reports (JCRs) [9].
– Articles published in English, Spanish, and Portuguese.
– Articles from journals with an impact factor ≥ 2.3, according to the Web of Science JCR [9].
– Articles presenting definitions for SOMRDFs or in vitro/in vivo studies related to SOMRDFs.
– Books published between 2020 and 2024 contribute definitions for SOMRDFs.
Exclusion criteria included:
– Reports referring to conventional drug release or administration routes other than oral.
– As a quality assessment criterion, original articles that do not provide experimental data supporting the type of oral release, such as in vitro dissolution profile, mathematical release models, or drug plasma concentration–time profiles, and those with a lack of coherence between methods and results.
These criteria were manually verified during screening and eligibility assessments.
A total of 4,693 records were initially identified, but 3,199 were removed early, mainly for being duplicates, which were identified using Zotero [10]. The remaining 1,492 records were screened by titles and abstracts, leading to the exclusion of 986 for not meeting the predefined inclusion and exclusion criteria. A second screening was performed by an independent researcher, and discrepancies were resolved by consensus with the participation of the lead researcher; this process resulted in the exclusion of 945 records and left 547 available for full-text reading. Quality assessment was applied to these reports, leading to the exclusion of 401, which resulted in 146 studies included in this research (Fig. 1). Dual review was also applied in all stages of the assessment.
2.3. Data extraction
From review articles, books, official documents, and compendia, terminology and definitions associated with SOMRDFs were extracted.
From original articles presenting in vitro/in vivo studies related to SOMRDFs, the following variables were collected: time of onset release, time to maximum release, maximum percentage released, and the mathematical model and/or technology used. For articles evaluating multiple formulations, only variables from the formulation identified by the authors as preferred were considered. Where the preference was not mentioned, the variables from all formulations were collected as a range. When data were not reported or could not be reliably extracted from graphs, the variable was marked as “no data”.
The extracted information was transferred to a Microsoft Excel [11] data matrix that also included the document title, authors, year, methods (where applicable), and data collected. The transfer of information was also subjected to dual review.
Original articles presenting ER formulations were grouped based on the SOMRDFs terminology cited, and variables were presented as the range of the grouped values or as the maximum reported, when applicable.
3. RESULTS
3.1. Terms associated with SOMRDFs according to health authorities in the Americas
Since special delivery technologies emerged, health authorities worldwide have needed to define and classify the different types of oral MR dosage forms. In this section, a compilation of such definitions by health authorities in the Americas is presented, organized chronologically and by institution.
In 1990, the United States Pharmacopeia (USP) defined MR pharmaceutical forms and their drug release characteristics—such as timing and/or location—as those designed to achieve therapeutic goals or provide convenience not possible with conventional formulations. The USP classified these systems into three categories:
– ER dosage forms: Those that release a dose allowing a twofold reduction in the frequency of administration when compared to an IR dosage form.
– DR dosage forms: Those that release discrete portions of the drug at times other than immediately after administration, although a fraction may be rapidly released conventionally. Enteric-coated dosage forms are the most common DR products.
– Targeted-release dosage forms: Those that release the drug at or near the site of desired physiological action and may have immediate or ER features [12].
Over time, the USP discontinued the term “targeted-release” as an official category, and the designation of MR was limited to two main types, ER and DR, as the terms used in official article titles. Throughout the different editions of the USP, equivalent terminology for these definitions has been gradually recognized. In the USP 30 NF 25 (2007), the terms SR, CR, and “prolonged-action” were cited as equivalents of ER [13]. By 2018, the USP 41 NF 36 acknowledged “repeat action” as another equivalent for ER dosage forms [14], and in 2019, the USP 42 NF 37 introduced “long-acting” as an additional synonym [15]. Meanwhile, for DR dosage forms, the expressions “enteric coated” and “gastro-resistant formulations” have been used over time by USP to describe formulations in which drug release is prevented in the stomach but promoted in the intestine.
The current USP (2025) definition of MR no longer refers to the site of drug release but rather focuses on its rate and timing, indicating that these parameters are altered compared to IR products. ER no longer implies a twofold reduction in the frequency of administration compared to an IR dosage form, but instead refers to formulations specifically designed to prolong drug release regardless of the dosing frequency [4].
In 1997, the FDA published the guidance document “SUPAC-MR: MR Solid Oral Dosage Forms”. In this document, MR dosage forms were classified into two types:
– ER: Products formulated to make the drug available over an extended period after ingestion, allowing a reduction in dosing frequency compared with a drug presented as a conventional dosage form (e.g., as a solution or an IR dosage form).
– DR: Products that release a drug (or drugs) at a time other than immediately following oral administration [16].
Years later, in 2014, the FDA guidance “Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs—General Considerations” stated that MR products include both ER (equivalent to CR and SR) and DR formulations. Although DR products are defined as MR dosage forms, the document notes that many behave like IR products once the intended delay has elapsed [17]. The 2022 version of this guidance maintains the same classification [18].
In 2007, the Oriental Republic of Uruguay, through Decree No. 12/007 (Official Gazette No. 27.165-A), approved technical recommendations for bioequivalence studies (Aprobación de las recomendaciones técnicas para la realización de estudios de bioequivalencia contenidas en el documento Intercambiabilidad de medicamentos), classifying MR systems into PR and DR. For the former, it was stated that they release the drug over a longer period after administration than IR forms, without any reference to a reduction in the frequency of administration. For DR products, it was highlighted that the onset of drug release is postponed until the product passes through the stomach due to an enteric coat, after which it behaves as an IR formulation [19].
The Brazilian Health Regulatory Agency (ANVISA) published the 5th edition of its pharmacopeia in 2010. In volume I, MR dosage forms were classified into two categories: PR and DR. Although ANVISA did not provide a general definition for MR formulations, it preferred the term PR over ER, and did not adopt alternative terms—such as SR, CR, or “repeat action”—commonly used by the USP and FDA.
According to ANVISA, PR refers to formulations that enable at least one reduction in dosing frequency compared with conventional forms. Additionally, DR formulations are defined as those resulting from a specific design or manufacturing method that postpones the release of the active substance. Gastro-resistant preparations are also considered a type of DR by ANVISA [20].
In Volume I of the 7th edition of the 2024 Brazilian Pharmacopeia, the same classification and definitions of MR formulations (PR and DR) were maintained, reaffirming that PR formulations are designed to achieve at least one reduction in dosing frequency compared to conventional dosage forms [21].
In 2013, the Republic of Costa Rica, through Decree No. 32470-S, “Technical Guide for the Application of Post-Registration Changes in Medicines with Therapeutic Equivalence (Guía Técnica para la Aplicación de Cambios Post-Registro en Medicamentos con Equivalencia Terapéutica)”, described MR dosage forms as pharmaceutical preparations in which the rate and/or site of drug release differs from that of conventional dosage forms. This modification is achieved through a particular formulation design or a special manufacturing method. MR dosage forms include “PR”, “enteric”, “pulsatile” release, and others. The definitions provided in this guide are detailed below:
– CR: A term that describes, without precision, the release of the active ingredient from any formulation designed to follow a predetermined kinetic release profile.
– PR: A formulation that does not release the total dose of the active pharmaceutical ingredient (API) immediately after administration but instead does so slowly enough to extend the dosing interval two or more times, with no initial fast dose.
– Repeated release: The API is released at time intervals, and plasma concentrations are similar to those of a conventional release dosage in each one.
– SR: A formulation that allows the rapid release of a fraction of API in the initial phase, followed by a gradual release of the remainder for a prolonged time, thereby minimizing high plasma concentration fluctuations [22].
Unlike what is observed in other entities, the Costa Rican guideline is the only one that explicitly distinguishes between PR and SR, based on the presence or absence of an initial rapid release. The Chilean Institute of Public Health, later, in 2018, presented the same classification as Costa Rica in its “MOVAL 01” guide [23].
The 7th edition, volume IV of the 2013 version of the Argentinian Pharmacopoeia explains that expressions such as “prolonged action”, “extended action”, and SR are regularly used to describe pharmaceutical forms. However, PR is encouraged to be used for official titles. Regarding DR forms, it specifies that they delay the release of the API until after it has passed through the stomach, which is again referred to as enteric-coated formulations. This version of the Argentinian pharmacopoeia remains in use [24].
The Ministry of Health and Social Protection of Colombia (MSPSC), along with the INVIMA, through Resolution 1,124 of 2016, established that MR products include both ER and DR dosage forms, and that ER are indistinctly known as CR, PR, and SR dosage forms. In this resolution, no formal definitions are suggested for any of the SOMRDFs [25].
In 2018, the guide “Studies on Bioequivalence of Solid Oral MR Medicines (Estudios de Bioequivalencia de medicamentos sólidos orales de liberación modificada)”, which is originally referenced in the norm NOM-177-SSA1-2013 [26] and released General Health Council of Mexico (Consejo de Salubridad General, CSG) of the United Mexican States, also stated that MR pharmaceutical forms are formulations in which the rate and/or the site of drug release differs from that of oral IR forms.
The definitions are as follows:
– DR: A condition in which the formulation allows for a delay in the release of the API, including gastro-resistant products. Key characteristics related to DR products include: the release of the drug occurs sometime after administration; the formulation is resistant to gastric fluids; once release begins, the formulation behaves as an IR form; there is only a delay in achieving measurable plasma concentration without extending the overall duration of the therapeutic effect; the formulations are usually coated or pH-dependent and are intended to delay release until the drug reaches the absorption site, where the pH allows its release.
– PR: A pharmaceutical form designed to make the active ingredient bioavailable for a longer period after its administration. In this system, it is mentioned that there are more types, such as “SR”, “ER”, “CR”, and “repeated” releases, but no explanation or distinction among these subtypes is provided. However, this guide affirms that there is no harmonization of terms used to describe the different systems of SOMRDFs; nevertheless, the classification is presented as an enunciative and non-limiting approach [27].
In the same year, 2018, Health Canada released the guidance document “Comparative Bioavailability Standards: Formulations Used for Systemic Effects” and defined MR dosage forms as drug formulations that differ from conventional products in the rate at which the drug is released. No classification is provided in the document (e.g., ER or DR), focusing instead on describing the different objectives that these formulations may have, such as delaying disintegration or dissolution, providing effective drug concentrations for a longer time, minimizing gastrointestinal or other adverse effects, reducing fluctuations in drug concentrations, and producing multiple peaks and troughs in the concentration-time profile after a single administration (i.e., multiphasic MR dosage forms) [28].
The Republic of Paraguay, through Resolution S.G. N-092 of 2020, established a classification of MR dosage forms into PR and DR. For PR, it is stated that it can also be called CR, although no complete definition is provided. Meanwhile, for DR, the resolution refers to formulations with gastro-resistant coating, which suggests that drug release is delayed until the product reaches the intestine [29].
The Republic of Ecuador follows the same classification as the Colombian government in the Resolution “ARCSA-de-2024-038-DASP” issued in 2024, maintaining ER and DR as the main categories for MR dosage forms [30].
In Figure 2, a summary is presented of the terms used to classify the SOMRDFs as provided by the different health authorities across the Americas.
 | Figure 2. Summary of terms used by health authorities in the Americas to classify SOMRDFs. [Click here to view] |
Over the years, the classification of MR pharmaceutical forms has remained largely consistent across regulatory entities. These authorities have also recognized the different terminologies used in literature and by marketing authorization holders (MAHs) as equivalent terms. However, two principal types are generally recommended: DR and ER (referred to as PR in most Spanish-speaking countries), which emphasize, respectively, the delay in the onset of release and the prolongation of the duration of the release to reduce dosage frequency. This consensus has been addressed through the evolution of USP definitions [1990–2025] [4,12–15], the classification from the FDA [1997–2022] [16–18], and those from Uruguay (2007) [19], Colombia (2016) [25], Mexico (2016) [26,27], Canada [28], Paraguay (2020) [29], Brazil [2010–2024] [20,21], and Ecuador (2024) [30].
3.2. Terms associated with SOMRDFs according to authors publishing in scientific journals
This section reviews the classification and definitions of the different types of SOMRDFs reported by authors in scientific articles and textbooks, selected according to the criteria described in the methods section.
In 1984, De Haan and Lerk [31] described and used CR as a collective term for any formulation in which the release rate is altered through galenic manipulations. They also agreed that oral drug products providing a longer duration of pharmacological effect are classified as SR, “prolonged acting”, and/or “repeat action” drugs. It is notable that instead of using the term “release” they chose “action” to classify some types of SOMRDFs. The authors indicated that there are slight differences between “prolonged acting” and SR preparations, but these were not clarified in the document. It was stated that it is challenging to classify products in these categories, and therefore, both terms are used interchangeably [31].
Later, in 1995, Buckley et al. [32]used the term CR to cover various methods that allow modification of drug release and therefore absorption, including transdermal administration products and oral preparations with “slow-release”, ER, and DR. Although the different types of release were not explicitly defined by the authors, it was reported that ER products maintain plasma concentrations for a longer time than “slow-release” products [32].
In 2002, Suñé [5], highlighted that the terminology used to define the SOMRDFs is broad and confusing, a point that motivated the present review. Nevertheless, the author presented several categories, each with a specific definition:
– SR forms: initially release enough drug to achieve the desired pharmacological response rapidly and subsequently release an adequate and constant quantity of drug to maintain the absorption rate equal to the elimination rate for a period, usually 10 to 24 hours. Therefore, these pharmaceutical forms exhibit zero-order release kinetics, resulting in constant plasma drug concentrations.
– ER forms: correspond to those formulations in which the drug is initially released in an amount sufficient to produce a therapeutic action or even in a small excess that is never harmful to the organism, followed by a slower release but at a rate that is not always equal to that for elimination. In other words, these pharmaceutical forms present a slow but non-constant release, producing plasma concentrations that fluctuate within the therapeutic zone, describing a wide curve.
– Repeated release forms: provide an initial dose of the drug and later release another similar dose.
– DR forms: release the API after a latency time, so that plasma levels of the drug remain zero until it reaches a specific region of the gastrointestinal tract where the release occurs [5].
As observed above, for this author, both SR and ER forms include an initial release phase, but SR aims to maintain constant plasma concentrations, whereas ER allows controlled fluctuations in plasma levels over time.
In 2015, a review by Patel and Patel [33] classified MR dosage forms into several categories, including ER, SR, DR, CR, “repeat action”, “prolonged-action”, and targeted-release. These dosage forms refer to products that alter the timing and rate of drug release. This text highlights some characteristics of each of them, as follows:
– ER forms: reduce the dosing frequency compared with IR forms.
– CR forms: enable a slow release of the drug over an extended period, but it is not possible to determine a precise release rate.
– SR forms: provide a specific and measurable delivery rate for an extended period.
– Prolonged-action forms: release the drug slowly and provide a continuous supply of the drug over an extended period.
– Repeat action forms: deliver a first dose, followed by a second release at a later time.
– DR forms: release a discrete portion of the drug at a different time after administration, although a small portion may be released immediately.
– Targeted-release forms: release the drug at or near the intended site of action, and may exhibit ER characteristics [33].
Based on these definitions, it can be interpreted that ER and CR are general classifications for SOMRDFs, while PR and SR are categories assigned to those where the rate of drug release is specifically determined.
In 2020, Trenfield and Basit [34] adopted the classification proposed by the USP in 1983, which includes ER, DR, and targeted-release. ER is described as providing at least a twofold reduction in dosing frequency compared with an IR product. Examples of this type of release include SR, CR, and “long-acting” formulations. DR products are described as releasing discrete portions of the drug at specific times after administration, without an explicit reference to a latency period. According to these authors, targeted-release may also behave as an IR product after the administration; examples include gastroretentive devices and colonic drug delivery systems [34]. As mentioned previously, the current USP does not consider targeted-release as part of SOMRDFs.
In 2022, Ducharme et al. [35] aligned with the classification and definitions proposed by Trenfield and Basit [34] for SOMRDFs, with some distinctions. The term “time-release drug products” was included as an equivalent to ER products. Gastroretentive devices and colonic drug delivery systems were excluded as examples of targeted-release products, and another type of SOMRDF was incorporated by the authors, the orally disintegrating tablets (ODTs). These are defined as formulations in which the drug is dispersed in saliva and swallowed with little or no water [35]. Notably, no other author in this review included this pharmaceutical form within the SOMRDFs categories. Likewise, neither the USP nor the FDA classifies ODTs as SOMRDFs [36].
In 2022, Soares et al. [37] defined PR as those formulations designed to release the drug more slowly than IR products, typically resulting in a long plasma concentration plateau period [37]. This definition is consistent with that proposed by Patel and Patel [33] for prolonged-action forms. No additional SOMRDFs definitions were reported by Costa et al. [37].
In 2024, Pather [6] recommended using only the terms ER (administered once or twice a day) and DR (referring to a lag time before release) and suggested that other terms and acronyms should be avoided when describing SOMRDFs. The author highlighted that alternative terms, such as SR, PR, CR, and timed-release, have been widely and interchangeably used for marketing purposes, and even though efforts have been made to standardize their use, this has led to confusion about what they actually mean [6]. Similar concerns have been raised by other authorities and authors, including the CSG from Mexico (2016) [26,27] and De Haan and Lerk [31].
In the same year, Kir, et al. [38] described CR products as formulations designed to prolong the therapeutic effect, maintain constant drug concentrations within the therapeutic range, reduce dosing frequency, minimize adverse effects, and improve patient compliance. The authors also emphasized that crushing SOMRDFs may compromise these therapeutic goals [38]. This definition is more comprehensive, as it incorporates clinical considerations and aligns with the descriptions provided by other authors for SR dosage forms by referring to a constant drug concentration. No other definitions of SOMRDFs were included in the publication.
Among authors, it is difficult to identify a clear consensus regarding a unified classification or consistent definitions of SOMRDFs. Researchers use a wide range of terms, often with overlapping or ambiguous distinctions, and some publications even propose using all these terms indistinctly. Moreover, a notable difference is observed compared with health authorities: the preference for the term “action” (e.g., “prolonged-action”) instead of “release”, which appears to refer not only to the duration of drug release but also the resulting duration of the therapeutic effect. In addition, the use of the term targeted-release is inconsistent with health authorities, who have already ceased to recommend it.
The arbitrary use of these terms creates confusion and hinders understanding for students, professors, and other stakeholders. A call to address this situation and simplify the terminology is necessary to prevent misinterpretation.
3.3. Use of terminology in research of SOMRDFs
This section reviews the use of the terms related to SOMRDFs in original research from different authors, analyzing dissolution profiles, plasma concentration curves, and other characteristics associated with these terms to identify inconsistencies or trends in terminology usage.
Out of 137 articles reviewed, 62 used the term “SR”, 37 used “CR”, 19 used “prolonged-action”, 10 used “DR”, 2 used “MR”, 5 used “ER”, 1 used the term “Ultra-long acting”, and 1 reported “Slow release”.
For most of the DR products (8 of 10 reports), the findings were consistent with definitions provided by health authorities and other authors. Initial release times ranged from 15 to over 180 minutes, while the maximum drug release varied from 65% to 100%, occurring between 120 and 720 minutes, depending on the formulation composition and the type of polymer used to modulate release. However, two articles described formulations with an immediate onset of release that were stated as DR products.
Table 1 summarizes the variability in onset and extent of drug release across DR formulations.
Table 1. Characteristics of DR formulations, according to the literature reports reviewed.
| Onset of release time (min) | Maximum percentage released | Time to maximum release (min) | Technology used | Reference (s) |
|---|---|---|---|---|
| 180 | 90 | 420 | Surelease (ethyl cellulose) | [40] |
| 30–120 | 80–99 | 120–720 | Methacrylic Acid Copolymer (Eudragit® L100-55) | [41] |
| 90 | 100 | 180 | Hydroxypropyl methylcellulose phthalate (HPMCP), polyvinyl alcohol, glucomannan and, polyethylene glycol 600 | [42] |
| 75 | 81 | 480 | Hydroxypropyl methylcellulose K15M, Carbopol 934P and, polyvinylpyrrolidone K30 | [43] |
| 120 | 65–100 | 180–480 | Eudragit® and poly (ethylene oxide), polyvinylpyrrolidone and, lactose monohydrate | [44] |
| 120 | 85–100 | 169 | Stearic acid (SA) pellets through hot melt extrusion | [45] |
| 105–120 | 100 | 155 | Microcrystalline cellulose (MCC) (Avicel PH-101), alginic acid, dextrin pellets through granulation, extrusion and spherization | [45] |
| 15–30 | 100 | 150 | Polyvinyl alcohol (PVA) and polylactic acid (PLA) filaments 3D-Printed Gastro-Retentive Floating Device (tablets) | [47] |
For oral ER dosage forms and their alternative terms (127 reports), most formulations exhibited an immediate onset of release, although some showed release beginning between 25 and 270 minutes after drug administration. The maximum percentage of drug released varied widely depending on the formulation, pH, polymers, and other factors, ranging from low (<10%) to high (>80%) release. The time to reach the maximum release is a key parameter for properly describing the release behaviour of any drug [38]; a broad range of times was observed across studies, from 120 to 12,000 minutes. Kinetic models were infrequently reported, being provided in only 58 of 127 reports. The zero-order, first-order, Higuchi, and Korsmeyer−Peppas models were the most applied for ER formulations. Additionally, 36 reports indicated the presence of a burst release phase.
Table 2 summarizes the characteristics of ER formulations, including those reported under alternative terminology. Overall, no distinctive features were identified among the different terms, suggesting that they are often used arbitrarily and could be used interchangeably.
Table 2. Characteristics of ER formulations, according to the literature reports reviewed.
| Dosage form terminology cited | Onset of release time (min) | Maximum percentage released | Time to maximum release (min) | Mathematical model reported | Reference(s) |
|---|---|---|---|---|---|
| PR | Immediate | 15–100 | 180–4,320 | Higuchi, Local regression, Korsmeyer-Peppas model, Brunauer-Emmett-Teller, Zero-order, First-order, Hixson-Crowell | [48–66] |
| CR | Immediate 60–120 | 30–100 | 300–4,320 | First-order, Bi-exponential Zero-order, Weibull model, Monolag, Higuchi, Hixson-Crowell, Korsmeyer-Peppas | [38, 67–100] |
| SR | Immediate 25–180 | 10–100 | 120–12,000 | Power law, Hixson-Crowell, Zero-order, First-order, Higuchi, Korsmeyer-Peppas | [101–140,47, 141–158] |
| ER | Immediate | 80–100 | 210–1,440 | No data | [159–162] |
| Ultra-long-acting | Immediate | 12–28 | 20,160 | No data | [163] |
| CR and DR | Immediate | No data | 1,440 | No data | [164] |
| Modified-slow release | Immediate | No data | 150–174 | No data | [165] |
| MR | 210–270 | No data | 1,440 | No data | [166] |
| SR and CR | Immediate 120 | 76–100 | 300–4,320 | No data | [167, 168] |
| Diffusion CR | Immediate | 20–55 | 360–720 | No data | [169, 170] |
| ER and SR | Immediate | 14–55 | 360–4,320 | No data | [171] |
| Slow-release | Immediate | 60–80 | 1,440 | No data | [172] |
| DR | Immediate | 20–85 | 2,880 | No data | [173] |
PR: Prolonged-release, CR: Controlled-release, SR: Sustained-release, ER: Extended-release, MR: Modified-release, DR: delayed-release (named as it by the cited authors). Overall, most ER formulations exhibit an immediate onset of release, wide variability in extent of release, and diverse kinetic models, suggesting that ER terminology is associated with the intent to prolong drug release and/or its clinical effect, rather than a specific dissolution pattern.
According to the health authorities from Costa Rica [22] and Instituto de Salud Pública de Chile [23], and the author Suñé (2002) [5], two specific characteristics are expected for SR dosage forms, as a special type of SOMRDF: to exhibit an initial burst release and to follow zero-order kinetics. However, only 19 out of 62 reports (31%) indicated a burst release, and only 5 reported zero-order release kinetics. Among other terms for SOMRDFs, 12% of the reports specified an initial burst release, and 10% stated zero-order kinetics. These findings support the conclusion that the term SR cannot be considered exclusively associated with these release behaviors.
The analysis of dissolution profiles from the reviewed reports led to the identification of cases where an initial burst release was not explicitly indicated but could be inferred from the data. For this evaluation, burst release was considered when two distinct release phases were observed in the profiles, with the initial phase related to the faster dissolution of the drug molecules [39]. Fourteen reports (23%) using the term SR were identified as exhibiting a burst release based on profile evaluation. Taking into consideration these reports together with the previously reported 31%, a total of 54% of the times that the term SR was used were associated with a burst release effect, while 46% neither mentioned nor exhibited this behaviour. A similar analysis was applied to reports using other SOMRDFs terminology; in this case, 41% of the reports appeared to present an initial burst release; when combined with the previously reported 12%, a total of 53% of the cases using terms other than “SR” were also associated with burst release. These findings reinforce the conclusion that the terminology used for SOMRDFs is often applied arbitrarily, and that SR is not consistently used as a distinct category of SOMRDF but rather as an equivalent term to “extended” and “prolonged”, as recognized by most health authorities.
To this stage of the review, the terminology proposed by health authorities appears clearer and more concise than that used by researchers, likely reflecting different objectives and contexts. For regulatory purposes, kinetic characteristics are not used as criteria for defining SOMRDFs; rather, the key factors are the onset and extent of drug release. In contrast, researchers tend to be more specific, showing interest in characterizing the effect of formulation variables on the drug release profile, which has led to the introduction of additional and sometimes redundant terms to refer to SOMRDFs. In our understanding, this lack of alignment may create confusion among healthcare professionals, patients, and students in chemistry and health sciences. Therefore, it is important for researchers and regulatory authorities to work together to establish harmonized terminology for SOMRDFs that promotes clarity, improves communication, and minimizes misinterpretation.
3.4. Terminology used by the regulatory authority and MAHs for the SOMRDFs in Colombia: case study
This section reviews the terminology employed by the Colombian regulatory authority (INVIMA) and by MAHs for SOMRDFs, using data from the “Unique Medicines Code (CUM)” database [174]. The analysis considered marketing authorization records that are currently valid, undergoing renewal, or temporarily suspended.
As of June 2025, there were 3,791 authorizations classified as some type of SOMRDFs by INVIMA. In general, this authority uses the terms “PR” and “DR”, consistent with the descriptions provided in the prior section. As mentioned in section 3.2, Resolution 1,124 of 2016 from the MSPSC suggested the use of the term “ER” for formulations that release the drug over a longer period than conventional products. Nevertheless, “prolonged”, which is the term most frequently used by INVIMA in the CUM database, is accepted as an equivalent designation under this regulation [25].
Remarkably, the term “enteric coated”, which, according to our review, corresponds to a type of DR dosage form, was used by INVIMA 72 times (≈ 1.9%). Additionally, nine records (≈ 0.2%) used the term “MR” as the pharmaceutical form without further specification of the type of modification, including records of marketing authorizations approved in 2025. This lack of specificity may create ambiguity in the interpretation of the dosage form for healthcare professionals, pharmacists, and patients.
Regarding MAHs, a variety of terms were identified in commercial product names to indicate the type of release: “PR” (46 times ≈ 1.2%), “DR” (36 times ≈ 0,9%), the expression “retard” (36 times ≈ 0,9%), “MR” (4 times ≈ 0.1%), “CR” (3 times ≈ 0.08%), and “programmed-release” (2 times ≈ 0.05%). The remaining 3,583 products (≈ 94.5%) did not include any reference to the type of release in their names. Interestingly, 18 products, including the expression “retard”, which is a word semantically related to “delayed”, were assigned by INVIMA the pharmaceutical form “PR”, whereas 15 other products named “retard” were not classified as SOMRDFs by the authority.
It was also observed that 23 products containing the expression “DR” in their brand name were classified by INVIMA as IR pharmaceutical forms, such as coated tablets or hard capsules. Similarly, one product labelled “PR granules” was not categorized as a SOMRDF in the CUM database.
In Table 3, a summary of inconsistencies found within the SOMRDFs report from INVIMA is presented.
Table 3. Summary of inconsistencies between product naming and regulatory classification.
| Product name | Pharmaceutical form according to health authority | n |
|---|---|---|
| Expression DR included | Not classified as MR | 23 |
| Expression “retard” included | PR or SR tablets | 18 |
| Expression “retard” included | Coated tablet without any reference to MR | 15 |
| Expression “XR” included | Unclassified | 5 |
| No type of MR included | Referred as MR without any type of specification | 5 |
| Expression PR included | Not classified as MR | 3 |
| Expression MR included | Referred as MR without any type of specification | 2 |
| Expression PR included | Referred as MR without any type of specification | 2 |
Source: database “Código Único de Medicamentos” from Colombian National Food and Drug Surveillance Institute (Instituto Nacional de Vigilancia de Medicamentos y Alimentos, INVIMA), report as of June 2025.
These findings underscore the inconsistency and indiscriminate use of terminology to name products within the industry and highlight the need for regulatory measures to ensure alignment between product naming and official classification of the pharmaceutical form. Furthermore, it is recommended that the regulatory authority in Colombia mandates labelling requirements to include the drug release type in the packaging of the product to minimize the risk of misinterpretation by prescribers and patients. This is particularly relevant when IR versions of the same API are also available, as misinterpretation could lead to prescribing or dispensing errors and potentially compromise patient safety.
 | Figure 3. Harmonized classification of SOMRDFs. [Click here to view] |
4. CONCLUSION
After a comprehensive review of information from health authorities in the Americas, research worldwide, reports from marketing authorization databases, and information from MAHs, the need for a harmonized terminology for SOMRDFs is reaffirmed. As a contribution to clarifying this matter, the following definitions and classification of terms for SOMRDFs are proposed:
Oral MR dosage forms: Formulations in which drug release is deliberately modified to either delay the onset or extend the duration of release.
– DR: Formulations that exhibit a latency in the release of the API after administration. They are generally intended for intestinal release, although a small fraction may be released before reaching the gut. These products behave similarly to IR formulations, as they do not prolong the drug effect. They are also known as gastro-resistant and enteric-coated formulations.
– ER: Formulations that release the API over a longer period than IR products. They use a variety of technological approaches to alter the pharmacokinetic profile of the drug and usually prolong the drug effect. Although zero-order release may be observed, it is not a mandatory characteristic. The following are discouraged legacy terms, rather than separated categories: “SR”, “CR”, “PR”, “timed-release”, “repeated-release”, and “programmed-release”.
Terms referring to “action” instead of “release” are strongly unsupported and should be avoided (e.g., “long-acting”, “repeat-action”, “prolonged-action”, and “ultra-long acting”).
Figure 3 provides a visual summary of the proposed classification of SOMRDFs resulting from this review.
5. LIMITATIONS
The review was limited by the search criteria (databases, keywords, and period included) and by the timing of the search. The review of documents from health authorities and compendia was limited to those from the Americas.
6. AUTHOR CONTRIBUTIONS
All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work. All the authors are eligible to be author as per the International Committee of Medical Journal Editors (ICMJE) requirements/guidelines.
7. FINANCIAL SUPPORT
This research and the APC were funded by Universidad del Atlántico, grant number QYF644-CIS2023.
8. CONFLICTS OF INTEREST
The authors report no financial or any other conflicts of interest in this work.
9. ETHICAL APPROVALS
This study does not involve experiments on animals or human subjects.
10. DATA AVAILABILITY
All data generated and analyzed are included in this research article.
11. PUBLISHER’S NOTE
All claims expressed in this article are solely those of the authors and do not necessarily represent those of the publisher, the editors and the reviewers. This journal remains neutral with regard to jurisdictional claims in published institutional affiliation.
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