Numerous health and social relationship problems, namely an increased risk of contracting HIV, mortality, crime, unemployment and impaired interpersonal relationships, are related to drug dependence, with opioids at the helm. For this reason, opioid addiction is considered a major public health problem [1] and is characterized as a ‘chronic relapsing disease’ and is a major concern for public health, as are drug and alcohol addictions [1, 2]. In addition to social support and psychotherapy, treatment of opioid dependence relies on medication intake. The three main opioid-dependence treatment categories include opioid agonists, opioid antagonists, and non-opioid medications. Naltrexone hydrochloride (API), one of the most commonly used medications relies on an opioid antagonist. It reduces opioid cravings; it can be administered outside the hospital setting and cannot be abused [3]. However, during treatment several patients often forget to take a dose, doubling the next dose to compensate. In some cases, this finding in the therapeutic levels is not being reached, while in other cases undesired (side) effects appear. For this reason, especially in the case of long-term treatments of numerous diseases, an extended dosing interval is recommended, so that the patient receives the drug, only once a day, instead of two or three times a day. Extended-release drug delivery systems can lead to drug plasma concentrations remaining within the therapeutic range for longer, reducing adverse effects and increasing patient compliance [4]. Existing studies have shown encouraging results and especially from alternative administrations, including extended release, achieving an increase in duration of action and better compliance, due to less frequent administration [5]. Thus, it is considered appropriate to further investigate whether the extended-release opioid addiction treatment approach, can be applied to naltrexone, which is one of the most common medications, and in which way to best serve the patients’ health and way of life. API has been selected for investigation, given that naltrexone can be administered per os for prolonged therapeutic effects [6]. The present study is in line with existing research [7-9] and compares the various extended-release forms of naltrexone tablets with the aim of finding the most suitable for release in the gastrointestinal tract. For this purpose, the tablets are prepared with three different excipients, namely inert substances included in the tablets in addition to the pharmaceutical substance. Excipients provide active ingredients with the desired properties and therefore formulate the drug by significantly influencing its quality and characteristics. The excipients used in this study are polyox or polyethylene oxide (ΡΕΟ), Eudragit or polymethacrylate-based copolymers and magnesium stearate. This supports that the appropriate excipients are chosen for extended/modified release within a predetermined period of time depending on the objective of the dosage form design and the desired way of releasing the active ingredient. In particular, the comparative experimental laboratory study of the three excipients demonstrates that, in terms of their ability to extend the release of naltrexone hydrochloride, the absence of the Eudragit leads to a faster release of the active substance.