Specific Drug Delivery System Research Articles

Combination of Pectin and Eudargit RS and Eudragit RL in the Matrix of Pellets Prepared by Extrusion - Spheronization for Possible Colonic Delivery of 5-Amino Salicylic Acid

Background: Different methods have been studied for targeting drugs to the colon, such as pH-based, time dependent and bacterially degradable systems. However, due to variations in physiological conditions of patients, one system alone could not be completely reliable on colonic drug delivery. Objectives: The aim of this study was preparation and evaluation of a novel colon-specific drug delivery system for 5-ASA (mesalazine) pellets using pectin as a microbially degradable polymeric carrier and Eudragit RS (ERS) and Eudragit RL (ERL) as time-dependent polymers. Materials and Methods: Formulations were constructed based on a multilevel full factorial design. Pellets were prepared via extrusion - spheronization and evaluated for physicochemical properties, image analysis, SEM, FT-IR, DSC and in vitro drug release studies in the simulated gastric fluid with pH = 1.2 (SGF), simulated intestinal fluid with pH = 6.8 (SIF) and simulated colonic fluid with pH = 6.8 in presence of pectinolytic enzyme (SCF). Results: It was shown that in the presence of pectin, formulations without ERL had a relative resistance to drug release in SGF. Pellets containing pectin and the least amount of ERS had the highest burst release effect in SCF. On the other hand, increasing in amount of ERS in the formulations caused a sustained drug release. Presence of pectin in formulations containing ERS and ERL caused sensitivity of formulations to pectinolytic enzyme which can suitable for a colon specific drug delivery system. Conclusions: It was shown that combination of pectin and eudragits can relatively control drug release in the upper GI. On the other hand, pectin degraded in the presence of pectinase and formulations were susceptible to the colonic media.

Modified Pulsincap of Ibuprofen - A Novel Approach for Chronotherapy

The aim of the present work was to develop colon specific drug delivery system for ibuprofen using natural polymers as carriers. We have investigated colon specific, pulsatile device to achieve time and site specific release of ibuprofen based on chronopharmaceutical considerations. The basic design consists of an insoluble hard gelatin capsule body, filled with ibuprofen surface solid dispersions and sealed with guar gum hydrogel plug. The entire capsule was coated with ethyl cellulose, so that the variability in gastric emptying time can be overcome and a colon specific release can be achieved. Surface solid dispersions (SSDs) of ibuprofen were prepared using natural polymers such as Guar gum (GG), Hupu gum (HG) and Xanthan gum (XG) in the weight ratios of 1:0.5, 1:1 and 1:2 by using solvent evaporation method. Physicochemical properties of the prepared SSD were characterized by FTIR and DSC. Optimized SSD were obtained by practical yield, drug content, solubility and dissolution studies and were selected for further fabrication of pulsincaps. Guar gum was used as hydrogel plug material to maintain a suitable lag period. The prepared pulsincaps were evaluated for in-vitro release. Pulsincap formulated with Ibuprofen-Hupu gum (PF3) at 1:2 ratio of surface solid dispersions showed highest drug release over the period of 12 hr and release was found to be Higuchi model kinetics. The present research study results have confirmed that the modified pulsincap of ibuprofen is a suitable device for the time dependent and site specific delivery to the colon segment of GIT.

Nanostructured thin films of degradable block copolymers and their applications

Nanopatterning using self-assembled thin films of degradable block copolymers (BCPs) has attracted considerable attention and inspired a variety of appealing applications in different research areas. To create useful nanopatterns for practical uses, controlling the orientation of the BCP microdomains is essential. The generation of oriented microdomains in BCP thin films will be discussed in this article. This discussion is followed by a review of methods that use polylactide-containing BCP (that is, polystyrene-b-poly(L-lactide) (PS-PLLA)) thin films to generate nanoporous PS after hydrolysis, which can be used for templated synthesis to create functional nanohybrids. The nanoporous PS thin films with well-oriented cylinder nanochannels can be used for pore-filling various ingredients to create specific drug delivery systems and optoelectronic devices. Moreover, by utilizing templated synthesis, nanoporous ceramics with a high-specific surface area and high porosity can be fabricated for optical applications using hydrolyzed gyroid-forming PS-PLLA as a template for the sol–gel reaction. In addition, the nanolithography applications using silicon-containing BCP (that is, polystyrene-b-polydimethylsiloxane) thin films, which can form inorganic nanoporous templates after oxygen plasma treatment, will be discussed in this review. Polymers that consist of two or more different components organized in distinct blocks give rise to intriguing and useful processes. By virtue of their similar properties, blocks of the same kind tend to aggregate. This ‘microphase separation’ phenomenon in turn organizes the bulk material in regular patterns. Subsequently removing one of the blocks selectively, by wet or dry etching, produces materials featuring well-organized, regular pores — sought after for a variety of applications ranging from drug delivery systems to optoelectronic devices. Rong-Ming Ho and co-workers from the National Tsing Hua University in Taiwan review how the blocks’ orientation can be controlled, focusing on materials made of polystyrene and either organic poly(L-lactide) (PS–PLLA) or inorganic, silicon-containing poly(dimethyl-siloxane) (PS–PDMS). For example, removing PLLA segments from the former by hydrolysis produces a nanoporous thin film that serves as a template for sol–gel reactions, whereas removing PS blocks from the latter gives a robust matrix that can be exploited as a mask in nanolithography. In this review, nanoporous thin-film template was obtained from the self-assembly of block copolymer PS-PLLA, at which the PLLA block can be hydrolyzed to form the nanopatterns. Nanoporous PS thin films with well-oriented cylinder nanochannels can be used for pore-filling with various ingredients to create specific drug delivery systems and optoelectronic devices. Moreover, nanoporous ceramics with high-specific surface area and high porosity can be fabricated for optical applications using hydrolyzed gyroid-forming PS-PLLA for templated sol–gel reaction. In addition, the formation of inorganic nanoporous templates from self-assembled PS-PDMS after oxygen plasma treatment and its corresponding applications in nanolithography will be discussed.

Design and development of liposomes for colon targeted drug delivery

Background: Local delivery to bowel tissue through oral administration is a challenging but a desirable goal to treat diseases like inflammatory bowel disease (IBD). Colon specific drug delivery system should be capable of protecting the drug en route colon.Purpose: Liposomes have shown potential to specific accumulation at inflammation site thus reduce toxicity; hence it can be used for effective treatment of IBD. Methods: Liposomes prepared using thin film hydration method. Statistical design was used for optimization. Colitis was induced using acetic acid. Inverted sac method was used as ex vivo model for IBD. Myeloperoxidase (MPO) activity and histopathology comparative study was carried out. Liposomes were formulated in enteric coated capsules to deliver the liposome specifically in initial segment of colon.Results: Particle size and entrapment efficiency were between 200 and 300 nm and 40 and 60%, respectively. In vivo and ex vivo study indicates higher accumulation of liposomes in colonic region as compared to pure drug. Enteric coated capsules delivered the drug after 5 h lag time.Discussion: Low particle size is attributed to low lipid content and stabilization due to surfactant. At higher cholesterol level, vesicles cannot reshuffle into smaller vesicles due to rigidization. Study shows higher accumulation of liposomes due to its lipoidal nature as compared to pure drug due to membrane transfer mechanism of drug thus MPO significantly lowers as compared to standard group (p < 0.05).Conclusions: Higher accumulation of liposomal drug in inflammatory area and specific release of liposomes by enteric coated capsules provide better option for the treatment of colonic disease.

Formulation and Evaluation of Colon Targeted Drug Delivery System of Levetiracetam using Pectin as Polymeric Carrier

Article history: Received on: 10/12/2012 Revised on: 29/12/2012 Accepted on: 15/01/2013 Available online: 28/01/2013 The aim of the present work was to develop and evaluate colon specific sustained release tablet using levetiracetam (LEV), microbially degradable polymeric carrier (pectin), coating material and matrix forming polymers. The colon targeted tablet was prepared by wet granulation technique using different percentage of pectin as matrix carrier, starch mucilage as a binding agent, HPMC K-100 as swellable polymer and coated with Eudragit polymers. Pectin, drug and physical mixture were evaluated for incompatibility study by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). All the batches of matrix tablet (F1-F4) were subjected for in-vitro dissolution in various simulated gastric fluids for suitability for colon specific drug delivery system. Tablets were evaluated for micromeritic properties of granules, physical properties, drug content, water uptake and erosion characteristics. F2 was optimized and subjected to coating based on evaluation results. The dissolution study of F2 revealed, in simulated intestinal fluid (SIF) release was 40.48% at the end of 6h and in simulated colonic fluids (rat caecal content) was 102.88% after degradation at the end of 8h. The colon targeted matrix tablet of LEV showed no change either in physical appearance, drug content or dissolution pattern after performing stability study for 3 months. The studies confirmed that, the designed formulation could be used potentially for colon delivery by controlling drug release in stomach and the small intestine.

Recent Advances of Mesoporous Silica Based Multifunctional Nano Drug Delivery Systems

Mesoporous silica materials have attracted much attention for their potential biomedical applications due to their tailored mesoporous structure, large surface area, good biocompatibility, and the ease of surface functionalization. In the past few years, the mesoporous silica based drug nanocarriers have become the research focus of many researchers. This article reviews the recent research advances of mesoporous silica based multifunctional drug delivery systems with targeting modification and bioimaging, and details the design, surface modification, and applications in drug delivery field of mesoporous silica based drug delivery systems with diverse morphologies(such as hollow/rattle-type, nanotubes, etc.). Finally, we analyze the existing problems in practical applications and outlook the future development trends of mesoporous silica based drug delivery systems(including the specific morphological, multifunctional hybrid, and biodegradable mesoporous silica drug delivery systems).

CPVA Grafted Poly(sodium 4-styrene sulfonate) and Studies on its Colon Specific for Chronotherapy of Nocturnal Asthma

The paper attempted to develop a colon specific drug delivery system using CPVA grafted poly (sodium 4-styrene sulfonate)(SSS), namely CPVA-g-PSSS microsphere, loaded with theophylline (TP) for chronotherapy of nocturnal asthma. The grafted CPVA-g-PSSS microspheres were prepared by surface-initiated graft-polymerization, and their surface charges were determined by testing Zeta potential. On this basis, the adsorption property of the grafted microspheres CPVA-g-PSSS for theophylline, namely drug loading ability, was mainly investigated, and the adsorption mechanism was explored. The in vitro release behavior of the drug-loaded microspheres was also examined at different pH value and in simulated gastrointestinal fluids. The experiments show the CPVA-g-PSSS microspheres exhibit strong adsorption ability (38.5 mg/g) for TP by driving of electrostatic interaction in an acidic medium. The in vitro release behavior of the drug-loaded microspheres is highly pH-sensitive. The in vitro release in simulated gastrointestinal (GI) fluid reveals that drug does not release in the stimulated gastric fluid (pH 1), while in the simulated colonic fluid (pH 7.4), a burst release phenomenon occurs, and 52% TP is released in one hour. An excellent colon-specific drug delivery system is developed to realize a lag time of drug release in 6 h runtime of upper gastrointestinal tract, which should be consistent with the demands of chronotherapy of nocturnal asthma.

Colon Targeted Drug Delivery System ? A Novel Perspective

In the recent years there is new development in field of colon specific drug delivery system. Colonic drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon like Crohn’s disease, ulcerative colitis, etc. but also for the systemic delivery of proteins, therapeutic peptides, anti-asthmatic drugs, antihypertensive drugs and anti-diabetic agents. New systems and technologies have been developed for colon targeting and to overcome pervious method’s limitations. Colon targeting holds a great potential and still need more innovative work. This review article discusses introduction of colon, need and approaches of colonic drug delivery, factor effecting colonic transition, colonic diseases and the novel and emerging technologies for colon targeting.

Solid lipid based nanocarriers: An overview / Nanonosači na bazi čvrstih lipida: Pregled

In the era of nanoparticulate controlled and site specific drug delivery systems, use of solid lipids to produce first generation lipid nanoparticles, solid lipid nanoparticles (SLN), became a revolutionary approach in the early nineties. The present review is designed to provide an insight into how SLN are finding a niche as promising nanovectors and forms a sound basis to troubleshoot the existing problems associated with traditional systems. Herein, authors had tried to highlight the frontline aspects prominent to SLN. An updated list of lipids, advanced forms of SLN, methods of preparation, characterization parameters, and various routes of administration of SLN are explored in-depth. Stability, toxicity, stealthing, targeting efficiency and other prospectives of SLN are also discussed in detail. The present discussion embodies the potential of SLN, now being looked up by various research groups around the world for their utility in the core areas of pharmaceutical sciences, thereby urging pharmaceutical industries to foster their scale-up.

An investigation of antileukemia activity of violacein-loaded dendrimer in Jurkat cell lines

Violacein, a bacterial pigment, has been reported to have in vitro antitumor effects. The objective of the current research was investigation of antileukemia activity of violacein – loaded dendrimer with ascorbic acid in Jurkat E6.1 cell lines as human acute lymphoblastic leukemia in a nanocomplex delivery system. Violacein was extracted and purified from Janthinobacterium lividum DSM1522T. Generation2 (PAMAM) dendrimer with extracted pigment and L-ascorbic acid were used as a nanocomplex delivery system.Chemical bonds between violacein and dendrimer were identified by fourier transform infrared (FTIR). Nanoparticles sizes were determined by scanning electron microscopy.The in vitro antileukemia activity of nanocomplex system was evaluated using MTT assay and caspase activity assay. FTIR assay results showed bands characteristic of the PAMAM dendrimer with violacein. Nanoparticles sizes were demonstrated almost 200 nm.The results showed dendrimer containing voilacein (IC50=4 μM) was almost 2 fold more efficient compared with free violacein. Flow cytometry studies of caspases activitiesdemonstrated that caspase -3, -7 and -8 caused apoptosis in 29, 34 and 41% of Jurkat E6.1 cells respectively. Cancer cells can uptake ascorbic acid higher than normal cells and it can operate specific drug delivery systems. This nanocomplex system can lead to pharmaceutical delivery at specific sites and reduce side effects. Key words: Violacein, dendrimer, antileukemia, jurkat cell line, Janthinobacterium lividum.

Colonic delivery of film coated meloxicam tablets using natural polysaccharide polymer mixture

Now days natural polysaccharides are extensively used for the development of solid dosage forms for delivery of drug to the colon. The objective of the present study was to develop a site-specific drug, single unit formulation allowing targeted drug release in the colon. Solid unit dosage forms were prepared using polysaccharides or synthetic polymer included xanthan gum, pectin, chitosan and Eudragit-E. Meloxicam was used as a model drug. The prepared tablets were enteric coated with Eudragit-S 100 to give protection in the stomach. The coated tablets were tested in-vitro for their suitability as colon specific drug delivery systems. The dissolution data so obtained illustrates that enteric coated tablets containing 3% chitosan as a binder, showed only 12.5% drug release in the first 5 h, which is the usual upper gastrointestinal transit time, whereas, tablets prepared using xanthan gum as binder, were unable to protect drug release under similar conditions. Solid formulations containing pectin as a binder formed time-dependent release formulations. 28% drug release was observed in the usual upper gastrointestinal tract conditions, when used in a concentration of 5.92% in the tablets.DOI: http://dx.doi.org/10.3329/icpj.v1i9.11617 International Current Pharmaceutical Journal 2012, 1(9): 264-271

Bactericidal activity of various antibiotics versus tetracycline-loaded chitosan microspheres against Pseudomonas aeruginosa biofilms

The discovery of biofilms in 1980’s has brought much interest to the study of the contribution of bacterial biofilms with many recurrent and chronic infectious diseases. In this study, we evaluated the utility of chitosan microspheres in delivering antibiotic in dosage form that could be effective against Pseudomonas aeruginosa (P. aeruginosa) biofilms. P. aeruginosa isolates were collected and identii¬ed using standard methods. A modii¬ed microtitre plate test was used to determine the bioi¬lm-forming capacity of the isolates. Moreover, bactericidal activity of various antibiotics vs. tetracycline-loaded chitosan microspheres against P. aeruginosa sessile and planktonic cells was tested. Results showed that, most P. aeruginosa strains (92.9%) were efficient biofilm producer-strains. There were differences in the antibiotic susceptibility of planktonic and sessile cell populations. Fluoroquinolones, aminoglycoside and tetracycline showed more potent activity (MIC50 was 0.8, 4.88 and 34.19 μg/ml, respectively) than penicillin, cephalosporin, clarithromycin and macrolides. Bioi¬lm growth was inhibited after 3 h treatment with 2x and 4x MICs and after 24 h treatment with MIC of tetracycline-loaded chitosan microspheres prepared by coacervation method than that prepared by water in oil emulsion method. This was correlated to the cumulative amount of tetracycline that was released from tetracycline-loaded chitosan microspheres prepared by coacervation method which released about 60% of tetracycline in the first 6 h and continued for 24 h. This in the clinical field may be translated into maintaining constant drug concentration for a prolonged period and maximize the therapeutic effect of antibiotics while minimizing antibiotic resistance and improved patient compliance. So, the use of tetracycline-chitosan microspheres may be a new strategy for the development of a specific drug delivery system to increase the efficacy of tetracycline against biofilm-associated P. aeruginosa infections. However, it would be appropriate to conduct clinical studies to confirm this. Key words: Bioi¬lm formation of Pseudomonas aeruginosa, tetracycline, antimicrobial susceptibility, microtiter plate method, drug-loaded chitosan microsphere.

In Vivo Human X-ray Investigation of Combined Polysaccharide Based Drug Delivery Systems Prepared for Colonic Delivery

The present investigation was aimed to assess the in vivo performance of combined polysaccharides based compression coated tablets for colonic delivery using X-ray study. Fast disintegrating core tablets containing barium sulphate was compression coated with guar gum (GG), locust bean gum (LBG) and hydroxyl propyl methyl cellulose (HPMC) in the ratio 3:3:4 with a coat weight of 400mg. The developed barium sulphate coated tablet was subjected for in vivo human X-ray study. X-ray study revealed that the tablet remained intact during its transit through upper part of gastrointestinal tract. The colon arrival time was found to be between 5-8 h. The disintegration of the tablet occurred in the colon between 14 to 16 h by the microflora present in the colon. In conclusion, results of X-ray studies revealed that GG and LBG along with HPMC was found to be promising coating materials for targeting drugs specifically to the colon. Keywords: Colon specific drug delivery system, colon targeting, compression-coat, diclofenac sodium, guar gum, locust bean gum, X-ray imaging and HPMC.

Controlled release of lipase from Candida rugosa loaded into hydrogels of N-isopropylacrylamide and itaconic acid

The series of poly(N-isopropylacrylamide-co-itaconic acid) hydrogels, with lipase from Candida rugosa as a model protein, were synthesized by free radical copolymerization. The composition of hydrogels was varied by monomers ratio, crosslinking agent concentration and amounts of lipase, which was loaded by in situ polymerization. All samples were characterized regarding morphology. The investigation of hydrogel swelling properties revealed their pH and temperature sensitive character. Protein loading efficiency, release profiles and the specific activity yield of the released lipase were also investigated as a function of hydrogel composition, protein content and pH, at the physiological temperature of 37 °C. Copolymers of N-isopropylacrylamide and itaconic acid presented high lipase loading efficiency. Another very important feature of these copolymers was that the protein release kinetic strongly depended on the pH value of the medium. The diffusion exponents values around 1 denoted that these hydrogel compositions could be adjusted to follow near zero-order kinetics. Namely, hydrogel formulations released low amounts of lipase at pH 2.20, but much higher released protein quantities were observed at pH 6.80 enabling these copolymers to be attractive candidates as site specific protein oral drug delivery systems.

Antioxidant potential of different melatonin-loaded nanomedicines in an experimental model of sepsis

Oxidative stress has been shown to play a major role in the complex pathophysiological processes leading to organ failure during sepsis. The aim of the present research was to evaluate the effect of different melatonin nanoparticle (NP) carriers in an experimental animal model of sepsis. Poly-D,L-lactide-co-glycolide (PLGA [NP-A]) and polyethylene glycol-co-(poly-D,L-lactide-co-glycolide) (PLGA-PEG [NP-B]) were used to obtain melatonin-loaded nanocarriers (10 mg/kg). Oxidative stress was measured in tissue homogenates by measuring heme oxygenase-1 (HO-1) expression, total thiol groups and lipid hydroperoxides (LOOH). In vitro NPs showed a long lag time followed by a controlled release of melatonin. All the different melatonin formulations restored total thiol group levels to those of controls in all the examined organs, with no significant changes among them. Both melatonin NP formulations significantly decreased LOOH levels when compared with sepsis vehicle animals. The stealth formulation NP-B was able to produce a more significant reduction in LOOH levels in the heart, lung and liver when compared with NP-A. No significant changes were observed between the two NP formulations in the kidney. Interestingly, HO-1 expression was differently affected following treatment with various melatonin formulations. The NP-B formulation was more effective in inducing HO-1 protein compared with free melatonin and NP-A, with the exception of the kidney. Taken together, our results show that melatonin possesses a significant antioxidant activity during sepsis and that it is possible to improve this ability by delivering the compound with specific drug delivery systems.

Low molecular mass chitosan as carrier for a hydrodynamically balanced system for sustained delivery of ciprofloxacin hydrochloride

Chitosan has become a focus of major interest in recent years due to its excellent biocompatibility, biodegradability and non-toxicity. Although this material has already been extensively investigated in the design of different types of drug delivery systems, it is still little explored for stomach specific drug delivery systems. The objective of the present investigation was to explore the potential of low molecular mass chitosan (LMCH) as carrier for a hydrodynamically balanced system (HBS) for sustained delivery of water soluble drug ciprofloxacin hydrochloride (CP). Various formulations were prepared by physical blending of drug and polymer(s) in varying ratios followed by encapsulation into hard gelatin capsules. All the formulations remained buoyant in 0.1 mol L⁻¹ HCl (pH 1.2) throughout the experiment. Effect of addition of xanthan gum (XG) or ethyl cellulose (EC) on drug release was also investigated. Zero order drug release was obtained from the formulations containing LMCH alone or in combination with XG, and in one instance also with EC. Our results suggest that LMCH alone or in combination with XG is an excellent material for stomach specific sustained delivery of CP from hydrodynamically balanced single unit capsules.

Formulation Development and Characterization of Guar Gum Microspheres for Colon Delivery

In the present work, colon specific drug delivery systems have been selected, to deliver the drug locally to colon for longer period of time. Cross-linked guar gum microspheres of model drug secnidazole were prepared by emulsification method and were evaluated for size and surface morphology by SEM, encapsulation efficiency, yield, swelling study. In vitro drug-release studies were performed in conditions simulating stomach-to-colon transit in the presence and absence of rat cecal contents. The marketed product was also compared for drug release profiles. The guar gum microspheres retard the release of drug in stomach but it facilitates the release of large amount of drug in the colon in the presence of rat cecal contents, as these have polysaccharides enzymes that degrade the guar gum in the colon. The release data shows that 44.4% of drug was released in the presence of rat cecal content release medium in 24 hours. Drug release data were fitted to different mathematical model to find release kinetic of drug. The stability studies were performed by storing the microspheres at different conditions of storage. The significance of differences was evaluated by analysis of variance (ANOVA). Differences were considered statistically significant at P < 0.05.

Formulation and in vivo evaluation of Floating Microspheres of Misoprostal

Prostaglandin (PG) has been reported to be an important protective and acid‐suppressive factor in the gastric mucosa. The objective of the study was to develop and evaluate a stomach specific drug delivery system for controlled release of Misoprostal a PE analogue for gastric ulcer induced NSAIDs. Floating microspheres were prepared by emulsification‐solvent evaporation method using ethylcellulose as a polymer, carbopol as mucoadhesive polymer. Ulcers were induced by the oral administration of absolute ethanol (5 ml/kg) to 24 h fasted Wistar male rats (n =8), weighing 200 g. Sodium bicarbonate solution, misoprostal solution and drug‐loaded microspheres were tested. Formulations were administered orally 1 h before the administration of ethanol. Prior to the oral administration, rats were anesthetized with ethylic ether. After 2 h of ethanol administration, animals were sacrificed; the stomachs were removed, opened along the greater curvature and examined for lesion measurements. Ulcer indexes (UI) were calculated. The in vivo evaluation showed that ulcer index values were 0.61 ± 0.14 for the sodium bicarbonate solution, 0.58 ±0.18 for the misoprostal and 0.11 ± .06 for the misoprostal‐loaded microspheres. The Kruskal‐Wallis test detected statistical differences (p =0.002) between the ulcer indexes. The multiple analyses (Student‐Newman‐Keuls) showed that the misoprostal loaded micro particles presented a gastric ulcer index statistically lower than the sodium bicarbonate solution (p = 0.001) and the misoprostal solution (p = 0.021). The percentages of ulceration inhibition were 31 and 75% after the administration of misoprostal solution and microspheres, respectively. In conclusion, the in vivo evaluation showed that the microspheres presented ulcer index lower than the solutions, showing that misoprostal‐loaded microparticles were efficient in protecting the stomach against ulcer formation.

IN VIVO EVALUATION OF MISOPROSTOL FLOATING MICROSPHERES

Prostaglandin (PG) has been reported to be an important protective and acid suppressive factor in the gastric mucosa. The objective of the study was to develop and evaluate a stomach specific drug delivery system for controlled release of Misoprostal a PE analogue for gastric ulcer induced NSAIDs. Floating microspheres were prepared by emulsification-solvent evaporation method using ethyl cellulose as a polymer, carbopol as mucoadhesive polymer. Ulcers were induced by the oral administration of absolute ethanol (5 mL/kg) to 24 h fasted Wistar male rats (n=8), weighing 200 g. Sodium bicarbonate solution, misoprostal solution and drug loaded microspheres were tested. Formulations were administered orally lh before the administration of ethanol. Prior to the oral administration, rats were anesthetized with ethylic ether. After 2 h of ethanol administration, animals were sacrificed; the stomachs were removed, opened along he greater curvature and examined for lesion measurements. Ulcer indexes (UI) were calculated. The in vivo evaluation showed that ulcer index values were 0.61 ± 0.14 for the sodium bicarbonate solution, 0.58 ±0.18 for the misoprostal and 0.11 ± 0.06 for the misoprostal-loaded microspheres. The Kruskal¬Wallis test detected statistical differences (p =0.002) between the ulcer indexes. The multiple analyses (Student-Newman-Keuls) showed that the misoprostal loaded microspheres presented a gastric ulcer index statistically lower than that of the sodium bicarbonate solution (p = 0.001) and the misoprostal solution (p = 0.021). The percentages of ulceration inhibition were 31 and 75% after the administration of misoprostal solution and microspheres, respectively. In conclusion, the in vivo evaluation showed that the microspheres presented ulcer index lower than the solutions, showing that misoprostal-loaded microspheres were efficient in protecting the stomach against ulcer formation. Key words: Misoprostal, microspheres, ulcer index,

COLON TARGETING APPROACHES: PAST, PRESENT AND FUTURE

The colon specific drug delivery system is gaining importance not only for local drug delivery of drugs but also for the systemic delivery of protein &amp; peptide drugs. Colon was considered as black-box as most of the drugs are absorbed from upper part of the GI tract. Colon targeting was aimed mainly because of less enzymatic activity and longer transit time. It also has drawbacks like less water content and presence of fecal content. To achieve successful colon targeted drug delivery, a drug needs to be protected from degradation, release and absorption in the upper portion of the GI tract and then to be ensured controlled release in the proximal colon. The various approaches that can be exploited to target the release of drug to the colon including formulation approaches through pH sensitive system are microbial triggered systems i.e., prodrugs and polysaccharide based system, timed release system, osmotically controlled drug system, pressure dependent release system, programmed pulsatile release system and others.