Controlled Release Microcapsules Research Articles

Preparation of Trichoderma asperellum Microcapsules and Biocontrol of Cucumber Powdery Mildew.

Microencapsulation is an important technique for protecting the viability and activity of microorganisms under adverse environmental conditions. To improve biological control, controlled-release microcapsules of Trichoderma asperellum were prepared and embedded in combinations of the biodegradable wall materials sodium alginate (SA). The microcapsules were evaluated for their ability to control cucumber powdery mildew in the greenhouse. The results showed that the highest encapsulation efficiency of 95% was obtained by applying 1% SA and 4% calcium chloride. The microcapsules provided good, controlled release and UV resistance, and could be stored for a long time. The greenhouse experiment revealed that the T. asperellum microcapsules had a maximal biocontrol efficiency of 76% against cucumber powdery mildew. In summary, embedding T. asperellum in microcapsules is a promising technique to improve the survivability of T. asperellum conidia. The T. asperellum microcapsules exerted significant biocontrol efficiency against cucumber powdery mildew. IMPORTANCE Trichoderma asperellum is widely found in plant roots and soil and has been used for the biocontrol of various plant pathogens; however, the control efficiency of T. asperellum is usually unstable in field trials. To improve the control efficiency of T. asperellum, in the present study, T. asperellum microcapsules were prepared using sodium alginate as wall material to reduce the effects of temperature, UV irradiation, and other environmental factors on its activity, and to significantly improve its biocontrol efficiency on cucumber powdery mildew. Microcapsules can prolong the shelf life of microbial pesticides. This study provides a new way to prepare a biocontrol agent against cucumber powdery mildew with high efficiency.

DESIGN AND EVALUATION OF BOSENTAN CONTROLLED-RELEASE MICROCAPSULES

Objective: The objective of the present work is to formulate and evaluate Bosentan controlled-release microcapsules using gum karaya and polyethylene oxide as polymers, sodium alginate and calcium chloride as encapsulating material and cross-linking agent and croscarmellose sodium as superdisintegrant. Methods: Bosentan microcapsules were prepared by the ionic gelation method. The prepared microcapsules were characterized by flow properties such as angle of repose, compressibility index, particle size and encapsulation efficiency and drug release profiles. Results: The prepared microcapsules were evaluated for angle of repose, compressibility index, % drug content, encapsulation efficiency and particle size. All the flow properties were within the specified IP limits. The drug content of microcapsules prepared by ionic gelation method by varying the polymeric concentration was found in the range of 121.62±0.41 to 124.99±0.51 mg. The encapsulation efficiency of Bosentan controlled-release microcapsules was found to be in the range of 59 % to 67%. Among all the formulations prepared, formulation B14 containing equal proportions (25 mg) of gum karaya and polyethylene oxide showed about 95% of drug release over a period of 12 h and were found to be suitable for extending drug release up to 16 h. Conclusion: Bosentan controlled-release microcapsules were prepared by ionic gelation method, which is a novel formulation that is helpful in the treatment of pulmonary artery hypertension (PAH).

Enhanced the entrapment and controlled release of Syzygium cumini seeds polyphenols by modifying the surface and internal organization of Alginate‐based microcapsules

The main objective of this study is using calcium alginate to encapsulate Syzygium cumini seed polyphenolic extract to maintain its stability and functionality. Calcium chloride was exploited as a cross‐linking agent to get the final form as calcium alginate capsules. Two different methods for drying of capsules were conducted; freeze‐dried (FD.C) and vacuum dried (D.C). Encapsulation efficiency for FD.C and D.C was 75.96 ± 0.68% and 70.20 ± 0.59%, respectively. The scanning electron microscopy (SEM) photographs and the mechanical properties indicated that the polysaccharide networks of D.C were strongly firm to prevent the release of total phenolic content (TPC) in gastric phase. FD.C showed fragile polysaccharide networks however, prevented the release of TPC in gastric phase and exhibited more release of TPC than D.C in intestinal phase. The microencapsulation process improved the thermal stability of the extract with 171.97°C and 180.36°C for FD.C and D.C, respectively. NOVELTY IMPACT STATEMENT: Sodium alginate in combination with calcium chloride was exploited to fabricate controlled release microcapsules. The fabricated microcapsules physically interacted with Syzygium cumin seeds polyphenols. The polyphenolic microcapsules were characterized with high ability to preserve polyphenols in gastric conditions and admitted with release of polyphenols in intestinal conditions. Moreover, the resulted microcapsules increased the thermal stability of grafted polyphenols. Thus, the obtained results would pave a new technique for medical purposes as controlled release systems or more stable capsules for food additive.

Controlled release Microcapsules for Oral Delivery of Aceclofenac: Formulation and Characterization

The aim of the present research work was to formulate microcapsules for rate controlled oral delivery of aceclofenac, using cellulose acetate phthalate (CAP) and ethyl cellulose (EC) as release retardant, and to evaluate the physicochemical properties. ‘Polymer deposition by emulsion-solvent evaporation’ technique was employed to produce microcapsules with CAP alone and with different proportions of CAP and EC, using acetone to dissolve the polymers. The formulations were characterized in terms of particle size, morphology, drug loading, entrapment efficiency, nature of flow and drug release. Infrared spectra and differential scanning thermograms confirmed the compatibility of drug with excipients and formulation process. Microcapsules were uniform, spherical, discrete and free flowing with the particle size varying from 397.32 to 526.06 μm. Average particle size increased with increase in proportion of polymer. High drug loading (19.12% to 42.84%) and entrapment efficiency (76.48% to 85.68%) were achieved, both the parameters decreasing with increasing fraction of polymer. The results of powder flow parameters like angle of repose, bulk density, tapped density, compressibility index and Hausner ratio confirmed that the powder was free flowing to enable direct capsule filling. The rate of drug release from microcapsules was found to be inversely related to the proportion of polymer. Substitution of a fraction of CAP with EC further slowed down the drug release rate, but the drug release was above 80% after 8 h. The drug release was dependent on concentration of aceclofenac in the core, with super case II transport mechanism. Delayed controlled release microcapsules of aceclofenac were successfully developed using ethyl cellulose and cellulose acetate phthalate, suitable for oral delivery.

Design and evaluation of controlled release losartan potassium microcapsules

BackgroundThe main objective of the present investigation is to design controlled release microcapsules of losartan potassium using Eudragit S100 as a release rate retarding polymer. MethodThe microcapsules were prepared by solvent evaporation method. The prepared microcapsules were characterized by various physical properties, such as flow properties and drug release profiles. ResultsThe microcapsules were discrete, spherical with free flowing properties. Losartan potassium is used as an antihypertensive belonging to angiotensin antagonist and it was successfully encapsulated with Eudragit S100. The morphology (Scanning Electron Microscopy), particle size distribution, entrapment efficiency and their release profiles were investigated. The yield was found to be maximum in case of solvent evaporation method. ConclusionThe microcapsules prepared with high proportion of polymer Eudragit S100 was found to extend the drug release up to 12 h.

Mucoadhesive controlled release microcapsules of indomethacin: Optimization and stability study

The aim of this project was to develop and optimize indomethacin microcapsules composed of multiple mucoadhesive polymers for high drug entrapment, good mucoadhesiveness and drug release in a controlled fashion over a longer period of time. Microcapsules containing sodium alginate, sodium carboxymethylcellulose, methylcellulose, Carbopol® 934 and hydroxypropyl methylcellulose were prepared by orifice-ionic gelation method. The effects of composition of microcapsules on drug entrapment efficacy, drug release and mucoadhesive character were determined by mixture statistical design. Most formulations exhibited good mucoadhesive property in everted intestinal sac test. Drug entrapment efficiency (68–94%) was dependent on the type of polymers. Drug release (92–100%) extended over 12 h. The optimized formulation resulted in drug entrapment efficiency of 89.3%, drug release of 94.8% and mucoadhesiveness of 30.4%. All formulations were stable for more than 1.5 years. The optimized mucoadhesive microcapsules are promising for controlled delivery of indomethacin with twice a day oral administration.

Chemical Mapping of Polymer Microstructure Using Soft X-ray Spectromicroscopy

Recently, synchrotron-based soft X-ray spectromicroscopy techniques have been applied to studies of polymer microstructure at the ~50 nm spatial scale. Functional group based chemical speciation and quantitative mapping is provided by near edge X-ray absorption fine structure spectral (NEXAFS) contrast. The techniques, sample data, and analysis methods of scanning transmission X-ray microscopy (STXM) and X-ray photoemission electron microscopy (X-PEEM) are outlined. The capabilities of STXM are illustrated by results from recent studies of (a) controlled release microcapsules and microspheres, (b) microcapsules being developed for gene therapy applications, (c) conducting polymer films studied in the presence of electrolyte and under potential control, and (d) studies of protein interactions with patterned polymer surfaces. In the latter area, the capabilities of STXM and X-PEEM are compared directly.

Preparation of monodisperse controlled release microcapsules.

Since the handling of many active agents in its pure form has many problems, microencapsulation is used to have better properties in the product. With the patented BRACE-Processes it is possible to encapsulate a very wide range of materials in monodisperse Microspheres or Microcapsules in a diameter range of 50-6000 microm with a very narrow size distribution. The Microsphere Units from BRACE can be customer tailored to the materials and all necessary specifications as FDA, GMP/GLP, EX, CIP, WIP etc. The throughput of the BRACE Microsphere Units ranges between 10 ml per h (small laboratory scale) up to over 1000 l per h (production scale) while the production cost are very low, especially if compared directly to competitive processes as spray-drying or fluidized bed coating.

Development and evaluation of verapamil resinates-loaded controlled release microcapsules using a binary polymer system in drug release rate modulation

The application of polystyrene-​divinylbenzene sulfonic acid-​based ion exchange resins as a carrier system for the sustained delivery of verapamil hydrochloride was primarily evaluated. A large degree of variation in the loading efficiencies (drug loaded: 19.17-​48.86​%)​, was obsd. between the different drug-​resin complexes depending on resin type and drug​/resin ratio. Upon comparing different carrier resins at drug​/resin ratio of 1:1, verapamil release in either 0.1 N HCl or phosphate buffer (pH 7.4) was in the order of Amberlite MB-​1 > Amberlite IRP-​69 (Na+) ≥ Amberlite IR-​120 (Na+) > Dowex-​50 W (Na+)​. For further retardation of the drug release rate, microencapsulation of the strongly acidic cation exchange resin (Amberlite IR-​120 (Na+)​) loaded with verapamil hydrochloride (drug​/resin ratio of 1:1, resinate drug content: 48.86​%, core​/coat ratio of 1:2) was carried out by means of a modified emulsion-​solvent evapn. / extn. technique (ESE​/E) using different coating polymers, namely Et cellulose (EC)​, cellulose acetate phthalate (CAP)​, cellulose acetate butyrate (CAB) as well as CAB​/polystyrene (PS) binary polymer systems. The effect of polymer type, polystyrene concn. and core​/coat ratio on the yield, size distribution as well as release characteristics and surface topog. of the microcapsules were investigated. The results obtained revealed that polystyrene utilization as a complementary wall material at a particular compn. of 70:30 (​%) of CAB to PS was found to improve greatly the microcapsule yield, reduce the av. microcapsule size and modulate the in-​vitro release of the entrapped drug. On the other hand, the entrapment efficiencies increased and the release rate decreased with increasing microcapsule size and​/or theor. drug loading of CAB​/PS (30​%) - microcapsules. Kinetic assessment of the release data using different math. models showed that the drug release from CAB or CAB​/PS (7.5​%)​-​microcapsules (core​/coat ratio of 1:2) was found to be best explained by a Fickian-​diffusion kinetics (a diffusion-​controlled model for a planar matrix)​, whereas the calcd. exponential release exponents (n values) of the empirical equation (Mr/M∞ = Ktn) indicated that the release behavior of CAB​/PS (30​%) - microcapsules was a non-​Fickian-​diffusion kinetics, confirming that a diffusion / chain relaxation-​controlled release mechanism was operative. Overall, this study demonstrated that the prepd. CAB​/PS microcapsules were capable of releasing their drug content gradually for an extended period of time, irresp. of variations in the pH of the gastrointestinal tract and exhibited slower release rates as compared with the com. sustained-​release product (Isoptin(SR) tablets)​.

β-Glucuronidase activity following complex coacervation and spray drying microencapsulation

The objective was to develop a microencapsulation process suitable for the controlled release of an active protein drug. β-glucuronidase was selected as a model protein and a combination of complex coacervation (gelatin/sodium alginate, gelatin/acacia and albumin/acacia) and spray drying was investigated. Coacervates were either spray dried or glutaraldehyde crosslinked to form microcapsules. Polyvinylpyrrolidone (PVP) and polyethylene glycol were investigated as potential coacervate enhancers and stabilizers. β-glucuroni-dase/polymer mixtures were spray dried to determine any polymer protective effects on protein activity. A BÜCHI 190 Spray Drier was used, β-glucur-onidase activity was determined using a Sigma Kit and microcapsule particle size was measured by Accusizer analysis (light blockage). All non-crosslinked coacervates investigated, with the exceptions of albumin/acacia and albumin/ acacia/β-glucuronidase/PVP, were unsuitable for spray drying as they rapidly phase separated and blocked the spray drier nozzle. β-glucuronidase activity in the albumin/acacia coacervates approximated to 99% prior to and 80% following spray drying. This can be compared to activities of approximately 30% and 68% when spray dried alone and with albumin, respectively, and of 18% in albumin/ acacia microcapsules crosslinked with glutaraldehyde. Microcapsule particle size was affected by coacervation pH, additives and spray drying. In vitro β-glucuronidase release was biphasic, with an initial burst release followed by a zero order release phase and continued over the 12 day study period. In conclusion, the spray drying albumin/acacia/PVP method described is useful for the preparation and collection of controlled release microcapsules with minimal loss of β-glucuronidase activity.

Insulin controlled-release microcapsules to prolong the hypoglycemic effect in diabetic rats.

A solvent evaporation process was employed for preparing insulin microcapsules by using biodegradable polymers [polylactic acid (PLA), HP-55] and non-biodegradable polymers [ethylcellulose (EC), ethylenevinyl acetate (EVA)]. The release behavior of insulin microcapsules in pH 7.4 phosphate buffer solution was undertaken by a continuous flow column method. Seven types of insulin microcapsules were respectively injected into the flanks of fasting-diabetic SD rats induced by streptozotocin. The glucose levels and insulin concentrations in the blood were periodically sampled from the tail and assayed by a glucose analyzer and RIA method. Body weights were measured twice per week. The release rate was controllably dependent on the polymer used. The PLA microcapsules could maintain normoglycemia only for five days, whereas the (PLA + 1%EVA) microcapsules exhibited two times the hypoglycemic effect of PLA microcapsules, but (PLA + 1%EVA) microcapsules treated with 4% wax extended the duration of hypoglycemic effects for two weeks. There was no significant effect for insulin-HP-55 microcapsules. The EC microcapsules prolonged the hypoglycemic effect for 15 days, however, the (EC + 1%EVA) microcapsules could maintain the same effect for up to three weeks. The slower the release rate of insulin microcapsules in vitro the longer the hypoglycemic effect of insulin microcapsules in vivo. A close relationship between in vitro release behavior and in vivo hypoglycemic efficacy of insulin microcapsules was obtained.

Assessment of in vivo drug dissolution by means of numerical deconvolution considering gastrointestinal availability

Numerical deconvolution has been applied for calculating the in vivo dissolution process. Due to intraindividual variations in drug absorption on different occasions of administration, a misleading picture of the actual amount dissolved in vivo can be obtained. A modified method for calculating the amount of drug dissolved in vivo is presented which considers both the reference formulation (weighting function) and the test formulation (response function) as equally available to the gastrointestinal tract, i.e. the place where the dissolution process actually occurs. The potential antipsychotic compound, remoxipride, administered as controlled release microcapsules, is used as a model system. It is demonstrated that if the deconvolution data are compensated for the amount of remoxipride absorbed from each formulation (test and reference), very good quantitative in vitro/in vivo dissolution correlations are obtained for each subject. The impact of considering both the conventional deconvolution curve and the modified one will be discussed.

An experimental study of the antitumour effect of bleomycin hydrochloride microcapsules

The controlled release behaviour of bleomycin hydrochloride microcapsules was investigated by an in vitro dissolution method and an in vivo antitumour test. Bleomycin hydrochloride microcapsules prepared using the highest cooling rate exhibited sustained release characteristics and its release rate obeyed a nearly zero order release kinetics. Microcapsules containing bleomycin hydrochloride were locally injected into the solid tumour of uterine cervix carcinoma bearing nude mice. Tumour growth was markedly inhibited by treatment using bleomycin hydrochloride microcapsules compared to the control group and the group receiving direct local administration of bleomycin hydrochloride. No significant differences in the changes of body weight after treatment were found between the control group and the treated group. These results suggest that controlled release microcapsules may be applicable as a drug carrier for delivery of antitumour agents in cancer chemotherapy.

Preparation of injectable controlled-release microcapsules by a solvent-evaporation process

The solvent-evaporation microencapsulation process can be used to prepare high-quality, injectable, controlled-release microcapsules containing as little as 1 wt.% drug to as much as 90 wt.% drug. This process is useful for the microencapsulation of water-soluble and water-insoluble drugs. When the process conditions are optimized, the process affords good yields of a free-flowing powder comprising smooth spherical particles. Using this process, a batch of microcapsules can be made to have a wide or narrow size distribution. The micro-capsules can have diameters from less than 1 μm to as large as 250 μm. During the early stages of a microcapsule development project, problems can often arise, and high-quality microcapsules are difficult to fabricate. Some of these problems and how to remedy them with respect to the solvent-evaporation process are discussed.

Statistical models for controlled release microcapsules: rationale and theory

The kinetics of release (or uptake) of material by a single microcapsule has been modelled. The model does not require concentric spherical shell geometry. The microcapsule wall is modelled separately as a lumped linear resistance to mass transport, the character of which is independent of conditions inside or outside of the capsule. The essential features of the model were developed by Aris [1] for describing diffusion through the pore structure of a catalyst particle. The model for single capsules has been incorporated into a statistical model for the kinetics of release (or uptake) of material from populations of microcapsules and related devices. Specific application is shown to populations of controlled release microcapsules where the individuals (1) release at constant rate during their lifetimes; and (2) release at an exponential rate ( ae - bt ). The model allows the individual capsules of a capsule population to differ in release kinetics, but in a given population the individual microcapsules areassumed to have kinetics of the same functional form. This functional form may be other than “constant rate” or “exponential rate”. The statistical model is applicable to populations of devices other than microcapsules.