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For several centuries, opium addiction has been a social problem all over the world. It has been prevalent in Iran from the Safavid era (1501-1736 A.D). During this period, Hakim Imad al-Din Mahmud ibn-Mas'ud Shirazi (1515-1592 A.D), also known as Imad was one of the Persian physicians who wrote one of the earliest books in the field of opium and addiction (called Afiounieh) in history. In this book, he introduced two sustained release rectal (suppository) and oral (pill) dosage forms for Muslim addicts who fast in the month of Ramadan. He aimed to formulate them for these people so that they could keep fasting by using the slow release drugs. In these formulations, his innovation has important impacts in the history of both addiction and pharmaceutical sciences.

From a historical perspective, this article describes the use of antipsychotic long-acting injections (LAI) in the treatment of schizophrenia, a disorder that was defined in the final years of the 19th century. An efficient treatment for schizophrenia was discovered only in 1952 with the introduction of chlorpromazine, a phenothiazine derivative. Fairly soon, antipsychotics became available as LAI. The first compounds were fluphenazine enanthate (1966) and decanoate (1968) whose development is attributed to G.R. Daniel, a medical director at Squibb & Sons. Other first-generation antipsychotics long-acting injections (FGA-LAIs) were introduced in a rapid succession in the 1960s and 1970s. FGA-LAIs made a key contribution to the development of community psychiatry. As neuroleptics emptied psychiatric hospitals, it was important to ensure that patients could be taken care of in outpatient facilities. FGA-LAIs prevented covert non-compliance. Compliance was further reinforced by the social and psychological support of patients. The introduction of second-generation antipsychotics (SGA) led to a loss of interest in FGA-LAIs. This is evidenced by a drop in the number of papers published on this topic. The interest in LAI was revived with the introduction of the first SGA-LAI in 2003. Four different preparations have been approved in the decade between 2003 and 2013. SGA-LAIs differ from FGA-LAIs in the technology that is used to produce the depot effect, and also in the treatment objectives. The rationale for using SGA-LAIs is not only to prevent relapses due to treatment interruption, but also to achieve more constant plasma levels in order to reduce side effects due to excessive plasma levels and loss of efficacy due to insufficient plasma levels. Also, treatment objectives are no longer limited to controlling acute symptoms. Treatment objectives now include the alleviation of negative symptoms and cognitive deficits that are key prognostic factors., (Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

By any measure, transdermal drug delivery (TDD) is a successful controlled release technology. Over the last 30+ years, a steady flux of transdermal products have received regulatory approval and reached the market. For the right compounds, TDD is an effective and preferred route of administration; for others, delivery across the skin makes no sense at all. Currently, the "rules" that govern (passive) TDD feasibility are clearly understood, and research activity is focused on novel approaches that strive to subvert skin's excellent barrier function, and broaden the range of active species amenable to percutaneous administration., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Over the past decades, significant progress has been made in the field of hydrogels as functional biomaterials. Biomedical application of hydrogels was initially hindered by the toxicity of crosslinking agents and limitations of hydrogel formation under physiological conditions. Emerging knowledge in polymer chemistry and increased understanding of biological processes resulted in the design of versatile materials and minimally invasive therapies. Hydrogel matrices comprise a wide range of natural and synthetic polymers held together by a variety of physical or chemical crosslinks. With their capacity to embed pharmaceutical agents in their hydrophilic crosslinked network, hydrogels form promising materials for controlled drug release and tissue engineering. Despite all their beneficial properties, there are still several challenges to overcome for clinical translation. In this review, we provide a historical overview of the developments in hydrogel research from simple networks to smart materials., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Controlled drug delivery technology has progressed over the last six decades. This progression began in 1952 with the introduction of the first sustained release formulation. The 1st generation of drug delivery (1950-1980) focused on developing oral and transdermal sustained release systems and establishing controlled drug release mechanisms. The 2nd generation (1980-2010) was dedicated to the development of zero-order release systems, self-regulated drug delivery systems, long-term depot formulations, and nanotechnology-based delivery systems. The latter part of the 2nd generation was largely focused on studying nanoparticle formulations. The Journal of Controlled Release (JCR) has played a pivotal role in the 2nd generation of drug delivery technologies, and it will continue playing a leading role in the next generation. The best path towards a productive 3rd generation of drug delivery technology requires an honest, open dialog without any preconceived ideas of the past. The drug delivery field needs to take a bold approach to designing future drug delivery formulations primarily based on today's necessities, to produce the necessary innovations. The JCR provides a forum for sharing the new ideas that will shape the 3rd generation of drug delivery technology., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Clinical experience has shown considerable potential benefits from long-term continuous medication for chronic or relapsing forms of schizophrenia. These benefits have not always been realised., Aims: To review the research literature in order to understand the problems of long-term medication and use of antipsychotic oral medication and long-acting injections (LAIs), and to place these in an historical context., Method: Review of literature., Results: Research showed that the potential success of LAI therapy depends on the quality of the follow-up service., Conclusions: Following the advent of second-generation oral antipsychotics confidence in the use of LAIs has eroded and that mistakes made in LAI use during the past century may be repeated.

This paper describes the earliest days when the "controlled drug delivery" (CDD) field began, the pioneers who launched this exciting and important field, and the key people who came after them. It traces the evolution of the field from its origins in the 1960s to (a) the 1970s and 1980s, when numerous macroscopic "controlled" drug delivery (DD) devices and implants were designed for delivery as mucosal inserts (e.g., in the eye or vagina), as implants (e.g., sub-cutaneous or intra-muscular), as ingestible capsules (e.g., in the G-I tract), as topical patches (e.g., on the skin), and were approved for clinical use, to (b) the 1980s and 1990s when microscopic degradable polymer depot DD systems (DDS) were commercialized, and to (c) the currently very active and exciting nanoscopic era of targeted nano-carriers, in a sense bringing to life Ehrlich's imagined concept of the "Magic Bullet". The nanoscopic era began with systems proposed in the 1970s, that were first used in the clinic in the 1980s, and which came of age in the 1990s, and which are presently evolving into many exciting and clinically successful products in the 2000s. Most of these have succeeded because of the emergence of three key technologies: (1) PEGylation, (2) active targeting to specific cells by ligands conjugated to the DDS, or passive targeting to solid tumors via the EPR effect. The author has been personally involved in the origins and evolution of this field for the past 38 years (see below), and this review includes information that was provided to him by many researchers in this field about the history of various developments. Thus, this paper is based on his own personal involvements in the CDD field, along with many historical anecdotes provided by the key pioneers and researchers in the field. Because of the huge literature of scientific papers on CDD systems, this article attempts to limit examples to those that have been approved for clinical use, or are currently in clinical trials. Even so, it is impossible to know of and include all such examples and to properly credit all the key people who helped to bring the various technologies and devices to the clinic. The author apologizes in advance for all omissions.

The second part of the XXth century have seen the creation of new systems of administration for drugs, including delayed formulation systems or prolonged-release formulations (PRF). It is first within the industry, and mainly in the USA, that such new formulations were developed, with the purpose to increase the duration of action for pharmaceutical active principles. Several approaches were proposed and developed, jointly with more and more sophisticated evaluation techniques. In France, PRF market increased progressively during the 1980's; it then decreased because of more severe restrictions by health authorities for new drug approvals. In French specialty reference book (Vidal) included 518 PRF in the year 2000, from which 121 were tablets and 118 were hard gelatine capsules.

The first controlled-release methodology was developed in 1962 and was based upon diffusion of small molecules (molecular weight less than 500) through the wall of silicone rubber tubing. The problem of controlled-release of large molecules such as proteins was not solved until more than a decade later, when it was discovered that microchannels formed around lyophilized proteins embedded in polymers such as ethylene vinyl acetate copolymer (EVA) and poly(hydroxyethylmethacrylate) (pHEMA), as water permeated through the polymer. These studies led to the development of a 5-year contraceptive implant, e.g., Norplant; rapid progress in the field of angiogenesis research; and a method for regulating cell shape and growth control in vitro.

At the present time, three poly(ortho ester) systems have been described. The first one was developed at the Alza Corporation and is prepared by the transesterification reaction between a diol and diethoxytetrahydrofuran. It is currently marketed under the trade name of Alzamer. A second poly(ortho ester) system, developed at SRI International, is prepared by the addition of polyols to the diketene acetal 3,9 bis (ethylidene 2,4,8,10 tetraoxaspiro [5,5] undecane). A third poly (ortho ester) system, also developed at SRI International, is prepared by a transesterification reaction between a triol and an ortho ester, followed by self-condensation of the reaction product. Major utility of poly(ortho esters) as bioerodible drug delivery devices resides in their acid sensitivity which allows preparation of devices with lifetimes ranging from hours to many months by using acidic or basic excipients physically incorporated into the matrix.