Recent Patents on Drug Delivery & Formulation (v.3, #1)

Drug Delivery Systems for Photodynamic Therapy by Ryan Donnelly, Paul McCarron, David Woolfson (1-7).
Photodynamic therapy (PDT) is a medical treatment in which a combination of a photosensitising drug and visible light causes destruction of selected cells. Over the past two decades, photodynamic therapy has enjoyed a period of intense investigation, both in the laboratory and in the clinic. Although still widely considered to be an experimental technique, its status and value within modern clinical practice continues to grow. The PDT field has, to date, been dominated by a small number of pharmaceutical companies and inhabited almost exclusively by clinicians and those involved in fundamental scientific research. True pharmaceutical formulation development has been limited, to some extent, by financial constraints. If PDT is to realise its undoubted potential in clinical practice it is important that awareness of the need for appropriate photosensitiser delivery systems is raised. Accordingly, this article deals with the innovations pertaining to drug delivery systems for photodynamic therapy as disclosed in recent patent literature.

The global burden of diabetes is estimated to escalate from about 171 million in 2000 to 366 million people in 2030. The routine of diabetes treatment by injection of insulin incurs pain and has been one major factor negating the quality of life of diabetic patients. The possibility of administering insulin via alternative routes such as oral and nasal pathways has been investigated over the years, but with insulin experiencing risks of enzymatic degradation and poor transmucosal absorption. This leads to the rising needs to develop new formulation strategies emphasizing on the assembly of insulin and excipients into a physical structure to maintain the stability and increase the bioavailability of insulin. Chitosan and its derivatives or salts have been widely investigated as functional excipients of delivering insulin via oral, nasal and transdermal routes. The overview of various recent patented strategies on non-injection insulin delivery denotes the significance of chitosan for its mucoadhesive and able to protect the insulin from enzymatic degradation, prolong the retention time of insulin, as well as, open the inter-epithelial tight junction to facilitate systemic insulin transport. The chitosan can be employed to strengthen the physicochemical stability of insulin and multi-particulate matrix. The introduction of chitosan coat or co-formulation of chitosan with cationic gelatin or electrolytes which provide solidified or partially crosslinked structures retain and/or enhance the positive charges of dosage form necessary to induce mucoadhesiveness. The chitosan is modifiable chemically to produce water-soluble low molecular weight polymer which renders insulin able to be processed under mild conditions, and sulphated chitosan which markedly opens the paracellular channels for insulin transport. Combination of chitosan and fatty acid as hydrophobic nanoparticles promotes the insulin absorption via lymphoid tissue. Attainment of optimized formulations with higher levels of pharmacological bioavailability is deemed possible in future through targeted delivery of insulin using chitosan with specific adhesiveness to the intended absorption mucosa.

Trends in Pharmaceutical Taste Masking Technologies: A Patent Review by Zelalem Ayenew, Vibha Puri, Lokesh Kumar, Arvind Bansal (26-39).
According to the year 2003 survey of pediatricians by the American Association of Pediatrics, unpleasant taste was the biggest barrier for completing treatment in pediatrics. The field of taste masking of active pharmaceutical ingredients(API) has been continuously evolving with varied technologies and new excipients. The article reviews the trends in taste masking technologies by studying the current state of the art patent database for the span of year 1997 to 2007. The worldwide database of European patent office(http://ep.espacenet.com) was employed to collect the patents and patent applications. It also discusses the possible reasons for the change of preferences in the taste masking technologies with time. The prime factors critical to the selection of an optimal taste masking technique such as the extent of drug bitterness, solubility, particle characteristics, dosage form and dose are briefly discussed.

Protein and peptide-based therapeutic agents have unique physiochemical properties such as high molecular weight, short half life, requirement of a sustained plasma level for the desired therapeutic effect, liable to physical and chemical instability by gastric enzymes and harsh acidic environment as well as first pass metabolism, which makes their delivery a challenge. The delivery of proteins and peptides using various routes of administration like oral, nasal, rectal, pulmonary, buccal, vaginal and transdermal route is found to exhibit limitations, poor permeability and degradation being major limitations. Use of parenteral route is found to overcome these problems but patient compliance is poor due to the need for frequent administration. Use of control delivery for these drugs using smart polymers seems promising as they overcome the limitations posed by other routes of delivery. Smart polymers increase patient compliance, maintain stability of the drug, and maintain drug level in therapeutic window and are easy to manufacture. Different types of smart polymerbased delivery systems, such as sensitive to temperature, phase, pH, electric charge, light, and biochemicals, and their application in controlling the release of the incorporated drug to obtain a sustained plasma level has been discussed. Smart polymers, however, face challenges with regard to high burst release, unpredictable behavior in later part of biphasic release profile, overall drug release kinetics, conformational stability during processing, and preserving biological activity after getting released. Several patents overcoming these inherent problems associated with smart polymers have been reviewed. At the end, the future direction and potential of smart polymer-based delivery system for drug delivery has been presented in brief.

Recent Advances in Oral Pulsatile Drug Delivery by Lida Kalantzi, Evangelos Karavas, Efthimios Koutris, Dimitrios Bikiaris (49-63).
Pulsatile drug delivery aims to release drugs on a programmed pattern i.e.: at appropriate time and/or at appropriate site of action. Currently, it is gaining increasing attention as it offers a more sophisticated approach to the traditional sustained drug delivery i.e: a constant amount of drug released per unit time or constant blood levels. Technically, pulsatile drug delivery systems administered via the oral route could be divided into two distinct types, the time controlled delivery systems and the site-specific delivery systems. The simplest pulsatile formulation is a two layer press coated tablet consisted of polymers with different dissolution rates. Homogenicity of the coated barrier is mandatory in order to assure the predictability of the lag time. The disadvantage of such formulation is that the rupture time cannot be always adequately manipulated as it is strongly correlated with the physicochemical properties of the polymer. Gastric retentive systems, systems where the drug is released following a programmed lag phase, chronopharmaceutical drug delivery systems matching human circadian rhythms, multiunit or multilayer systems with various combinations of immediate and sustained-release preparation, are all classified under pulsatile drug delivery systems. On the other hand, site-controlled release is usually controlled by factors such as the pH of the target site, the enzymes present in the intestinal tract and the transit time/pressure of various parts of the intestine. In this review, recent patents on pulsatile drug delivery of oral dosage forms are summarized and discussed.

Site Specific Chronotherapeutic Drug Delivery Systems: A Patent Review by Nitin Saigal, Sanjula Baboota, Alka Ahuja, Javed Ali (64-70).
Oral dosage forms are known to provide a zero order or first order release in which the drug is released at a substantially steady rate of release per unit of time. However, there are instances where maintaining a constant blood level of a drug is not desirable. In such cases a pulsatile drug delivery may be more advantageous. Pulsatile drug delivery systems can be classified into site-specific systems in which the drug is released at the desired site within the intestinal tract (e.g., the colon), or time-controlled devices in which the drug is released after a well-defined time period. Environmental factors like pH or enzymes present in the intestinal tract control the release of a site-controlled system whereas the drug release from time-controlled systems is controlled primarily by the delivery system and not by the environment. The delayed liberation of orally administered drugs has been achieved through a range of formulation approaches, including single or multiple unit systems provided with release-controlling coatings, capsular devices and osmotic pumps. Our aim in this review is to outline the rational and prominent design strategies behind site-specific oral pulsatile delivery. The present article provides a good patent review regarding the Site Specific Chronotherapeutic Drug Delivery Systems.

CNS Drug Delivery Systems: Novel Approaches by Shadab Pathan, Zeenat Iqbal, Syed Zaidi, Sushma Talegaonkar, Divya Vohra, Gaurav Jain, Adnan Azeem, Nitin Jain, Jigar Lalani, Roop Khar, Farhan Ahmad (71-89).
The brain is a delicate organ, and nature has very efficiently protected it. The brain is shielded against potentially toxic substances by the presence of two barrier systems: the blood brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB). Unfortunately, the same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Despite aggressive research, patients suffering from fatal and/or debilitating central nervous system (CNS) diseases, such as brain tumours, HIV encephalopathy, epilepsy, cerebrovascular diseases and neurodegenerative disorders, far outnumber those dying of all types of systemic cancers or heart diseases. The abysmally low number of potential therapeutics reaching commercial success is primarily due to the complexity of the CNS drug development. The clinical failure of many probable candidates is often, ascribable to poor delivery methods which do not pervade the unyielding BBB. It restricts the passive diffusion of many drugs into the brain and constitutes a significant obstacle in the pharmacological treatment of central nervous system (CNS) disorders. General methods that can enhance drug delivery to the brain are, therefore, of great pharmaceutical interest. Various strategies like non-invasive methods, including drug manipulation encompassing transformation into lipophilic analogues, prodrugs, chemical drug delivery, carrier-mediated drug delivery, receptor/vector mediated drug delivery and intranasal drug delivery, which exploits the olfactory and trigeminal neuronal pathways to deliver drugs to the brain, are widely used. On the other hand the invasive methods which primarily rely on disruption of the BBB integrity by osmotic or biochemical means, or direct intracranial drug delivery by intracerebroventricular, intracerebral or intrathecal administration after creating reversible openings in the head, are recognised. Extensive review pertaining specifically, to the patents relating to drug delivery across the CNS is currently available. However, many patents e.g. US63722506, US2002183683 etc., have been mentioned in a few articles. It is the objective of this article to expansively review drug delivery systems for CNS by discussing the recent patents available.

Patent Selections by Publishers (90-93).
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