Controlled release

Sintering is defined as the thermal treatment of a powder or compact at a temperature below the melting point of the main constituent, for the purpose of increasing its bond strength. This concept in pharmaceutical science is relatively new, but research works relating to this process have been growing. Sintering has been described as the mechanism for the strengthening of the mechanical properties of consolidated pharmaceutical powders at elevated temperatures, for solid-bond formation during tablet compression, and for thermal curing of polymer-latex film -Coatings. The changes in the microstructures, Hardness, Friability, Wettability, disintegration time and dissolution rate of tablets stored at elevated temperature were also described as a result of sintering. Controlled release oral dosage forms were developed by sintering the polymer matrix by exposing to temperature above glass transition (Tg) point of the polymer. In the application of thermal sintering technique to the formulation of controlled release dosage form, the main research focus has been on the influence of sintering on the alteration of the microstructures in a polymeric matrix and the release of the active ingredients from the matrix.

Microsponge is unique drug delivery technique used for topical controlled drug delivery system as well as oral controlled drug delivery system. Microsponges are highly porous surface polymeric microspheres.  A well typical Microsponges (25 µm) can have up to 250000 pores approximately, due to  they also  give prolonged  release of active ingredients with continuously and reduce side effect, enhanced the stability of active ingredients. Mostly liquid – liquid suspension polymerization and quasi-emulsion diffusion methods are used for preparation of microsponges with different polymer such as Ethyl cellulose, Eudragit RS- 100, Eudragit S-100 and Eudragit E-100, Eudragit L-100, acrylic polymer etc used as formulation. Various therapeutics agents are loaded into Microsponges and then consolidate into different formulation like as gel, cream, and tablets. Drug is released from microsponges by different trigging system such as pressure system, solubility system, temperature change and pH triggered system. Various process parameters like concentration of drug and polymer, concentration of surfactants, volume of internal and external phase etc. affect the particles size, production yield, encapsulation efficiency and release of drug. In market different Microsponges based product are available such as NeoBenz®Micro, Neo®MicroSD, NeoBenz®Microwash,  Retin A Micro,  Retinol 15 Night cream, EpiQuin Micro and Retinol cream etc.

Zidovudine (AZT) is an antiretroviral drug with activity against Human Immunodeficiency Virus (HIV) Type 1. However, only temporary and limited benefits are observed in HIV infected patients treated with zidovudine alone or in combination with other antiretroviral drugs. Upon oral administration, it exhibits dose dependent toxic effects such as hepatotoxicity, hyperglycemia, hyperlipidemia, lactic acidosis, lipodystropy, osteonecrosis. These side effects often require dosage reduction or even cessation of treatment. Hence, in the present work an attempt is being made to develop a stable drug delivery system for zidovudine in the form of controlled release microbeads incorporated with different types of waxes. Wax incorporated microbeads of Zidovudine were prepared by melt extrusion-ionotropic gellation method. A series of tests have been carried out to characterize the microbeads in vitro, including particle size distribution, SEM analysis, loading parameters, in vitro release studies and stability studies. Compatibility studies proved that there was no interaction between zidovudine and different waxes used. Zidovudine beads were roughly spherical in nature, which was confirmed by Scanning electron microscopy. Zidovudine loaded beads with normal frequency distribution were obtained. A maximum of 74.65% drug entrapment efficiency was obtained. The in-vitro performance of Zidovudine beads showed sustained release up to 24 hrs depending on the wax concentration. Finally it can be concluded that the formulated matrix type microbeads with bees wax were more feasible and effective than carnauba wax beads in encapsulating zidovudine and thereby increasing the effectiveness of the drug.

In the present study, an attempt was made to develop the transdermal drug delivery systems of Fluvastatin sodium using transfersomes incorporated in a gel, which will control the release of drug, increasing the bioavailability of the drug and thus decreasing the dosing frequency of the drug.  It was designed by encapsulating the drug in various transfersomal formulations composed of various ratios of Soya Lecithin: Span 80 or Tween 80 or sodium deoxycholate. The transfersomes were prepared by rotary evaporation sonication method. Lipid:surfactant ratio of 90:10 is  found to be more effective when compared to other ratios . Experimental results of the present study showed that deformable lipid vesicles improve the transdermal delivery, prolong the release, and improve the site specificity of the Fluvastatin sodium. The drug diffusion studies showed that the prepared transferosome vesicle follows zero order kinetics and mechanism of drug diffusion follows peppas model.

Microsponges are tiny, uniform, micro-porous polymeric beads and spherical in shape. It has the interconnected voids. The particle size of it ranges between 5-300μm. The porous surface of non-collapsible structure of microsponges helps to deliver the active ingredient in controlled manner. Diclofenac Sodium is a Non-steroidal anti-inflammatory drug. The plasma half-life of Diclofenac is 1-2 hrs which increases the dosing frequency and this drug also causes the gastrointestinal irritation. Therefore the purpose of present investigation was to design suitable controlled release Diclofenac Sodium microsponges which can reduce the dosing frequency and gastric irritation. In the present work, Diclofenac Sodium loaded eudragit microsponges were prepared using quasi emulsion solvent diffusion method. Different drug: polymer ratios were used to formulate the microsponges. The compatibility of the drug with polymer was established. Surface morphology of the microsponges was examined using scanning electron microscopy. Production yield, loading efficiency, particle size analysis, and in-vitro release studies were carried out. In-vitro release study showed that the release of drug was in controlled manner and it was increased with increase in drug to polymer ratio up to certain limit.

The drug delivery through the skin to achieve a systemic as well as local effect of a drug is known as Transdermal drug delivery system. Its main advantage includes controlled drug release with minimum side effects, improved bioavailability and many more. The human skin is readily accessible surface for drug delivery. For penetration of drug through the skin the stratum corneum is the main barrier. So to avoid the stratum corneum and to increase the flux through the skin membrane different techniques of penetration enhancement are used.  This review mainly represents different factors affecting Transdermal bioavailability, technologies for developing Transdermal drug delivery system, different evaluation tests for Transdermal patches, different methods of preparation of TDDS, recent techniques for enhancing Transdermal drug delivery system.

The Microsponge Delivery System (MDS) is a unique technology used for controlled release and prolonged topical administration. Due to the difficulty that arouse in the release of the active ingredient over an extended period of time the fundamental need for the Microsponge technology arouse. The MDS consists of macroporous beads typically 10 – 25 microns in diameter loaded with the active pharmaceutical ingredient. When applied to the skin the MDS releases its active ingredient on a time mode and also in response to different stimuli like rubbing, temperature, pH etc. This technology is currently being used in sunscreens, skin care, cosmetics and prescription products.  It offers entrapment of ingredients and is believed to contribute towards reduced side effects, improved stability, increased elegance and enhanced formulation flexibility. Innumerable studies have confirmed that microsponge systems are non irritating, non mutagenic, non allergic and non toxic. Microsponges are used mostly for topical drug delivery and have been recently used for oral administration and tissue engineering.

Over the past 30 years greater attention has been focused on development of sustained or controlled release drug delivery. MEMS has been identified as one of the most promising technologies for the 21st century and has the potential to revolutionalize both industrial and consumer products by combining silicon based microelectronics with micromachining technology. MEMS based drug delivery devices have become commercially feasible due to converging technologies and regulatory accommodation. These products have the potential to completely control drug release, meeting requirements for on-demand pulsatile or adjustable continuous administration for extended periods. MEMS technology involves integration of mechanical elements, sensors, actuators and electronic elements on common silicon substrate through microfabrication technology.

  Stress is a biological response to aversive conditions that tend to threaten or perturb the homeostasis of the organisms. Stress is one of the basic factors in the etiology of number of diseases and stress has been postulated to be involved in pathogenesis of various diseases, such as psychiatric disorders like depression and anxiety, immune suppression, endocrine disorder like diabetes mellitus, impotency, cognitive dysfunction, peptic ulcer, ulcerative colitis and cardiovascular disorder like atherosclerosis and hypertension. So a mixture of herbal extracts like Arjuna, Ashwagandha, Brahmi and Shankhapushpi in equal ratios was microencapsulated using different types of wall polymers by non solvent addition method. Microcapsules were evaluated for their percentage yield, percentage actual drug content, percentage extract entrapment efficiency, flowability and drug release kinetics. Kollicoat SR 30 D and aluminium stearate were observed as effective in prevention of particle aggregation during phase separation.  Microcapsules were shown controlled drug release pattern for 12 hours due to the presence of Eudragit RS 100 and Eudragit RL 100. Both these wall polymers are responsible for controlling the drug release from microcapsules through diffusion in phosphate buffer medium having pH 7.4.

  Microsponge can be effectively incorporated into topical drug delivery system for retention of dosage form on skin, and also use for oral delivery of drugs using bioerodible polymers, especially for colon specific delivery and controlled release drug delivery system thus improving patient compliance by providing site specific drug delivery system and prolonging dosage intervals. Microsponge drug delivery systems offers entrapment of ingredients and is believed to contribute towards reduced side effects, improved stability, reduces systemic exposure and minimize local cutaneous reactions, increased elegance, and enhanced formulation flexibility. Topical preparations have some disadvantages like unpleasant odour, greasiness and skin irritation and fail to reach the systemic circulation this problem is overcome by microsponge delivery system. Microsponge formulations are stable over range of PH 1 to 11; Microsponge formulations are stable at the temperature up to 1300C; compatible with most vehicles and ingredients.  The present review introduces Microsponge technology along with its synthesis, characterization, programmable parameters and release mechanism of MDS.