Residence Time In Stomach Research Articles

Advancement in gastro retentive floating tablet: an updated review

The widespread use of oral dose forms in disease treatment may lead to inadequate pharmacokinetic properties due to rapid transit through the gastrointestinal tract. This makes it challenging to achieve therapeutic levels in situations where the medicine is barely soluble. Studies have been conducted to identify formulations that enhance these characteristics while extending stomach residence time, with gastro retentive controlled drug delivery systems being beneficial. This study evaluates recent developments in FDDS, focusing on how these systems function to make dosage forms float in stomach fluid for gradual release, better gastric retention, and improved bioavailability of oral medicine. It discusses the pharmaceutical importance of GRDDS, stomach physiology, and factors controlling gastric retention. The review also discusses the preparation of GRDDS, polymeric materials, dosage form evaluation, and comparisons between conventional and GRDDS. In this abstract, we will keep an eye on updated review on recent advancement in gastro retentive floating tablet.

Recent Advances in Gastro Retentive Drug Delivery Systems

The issues with oral conventional dose forms can be resolved with the use of gastroretentive drug delivery systems (GRDDS). GRDDS is a way to prolong the stomach residence time, which allows for the release of drugs and the possibility of local or systemic effects in the upper gastrointestinal tract. To enhance treatment, some potent medications are employed with gastro-retentive dose forms for longer. By producing a high concentration of medication in the stomach that can be sustained for an extended amount of time, gastroretentive formulations (GRFs) greatly improve stomach pharmacotherapy. As a result, a wide range of dosage forms have been developed for medications that break down at alkaline pH but remain stable at acidic pH. Therefore, medications have limited absorption.

A Review for Gastro - Retentive Drug Delivery System

Inadequate pharmacokinetic properties may be connected with the widespread use of oral dose forms in disease treatment. Because of the formulation's rapid transit through the gastrointestinal tract (GIT), it can be challenging to achieve therapeutic levels of the medicine in specific situations when it is barely soluble; In addition, some medications must work locally due to a gastric disease, although they only last a short period in the stomach. Numerous studies have been done to identify formulations that can enhance all of these characteristics while extending stomach residence time. Many orally delivered medications advantageous for from the extended stomach retention time provided by gastroretentive controlled drug delivery systems.With a focus on current methods for extending stomach residence duration, the study's objective was to examine, gather, and present the preceding and contemporary literatures in a shorter format. The current review briefly discusses the need for GRDDS., Pharmaceutical importance’s of GRDDS, Physiology of stomach, Stomach functionalities, Approaches of GRDDS, factors controlling gastric retention, advantages , disadvantages, Method of preparation of Gastro-retentive Multiparticulate system, Polymeric material in gastroretentive formulations, Evaluation of Gastroretentive dosage form, comparsion between Conventional and Gastroretentive drug delivery system.

Gastroretentive Drug Delivery System in Cancer Chemotherapy.

Chemotherapy for stomach cancer often includes several side effects. The primary reasons for the failure of such treatment approaches are low drug concentrations in target tissues and a short stomach residence time. Gastroretentive controlled drug delivery systems improves the therapeutic performance of chemotherapeutic drugs following oral administration because of the longer gastric retention time. The goal of this study was to find suitable gastroretentive formulations that might be used for the localized treatment of stomach cancer. The purpose of this study is to summarize current advances in gastro-retentive drug administration for oral chemotherapy, with a focus on floating, mucoadhesive, and swellable systems. This article also discusses the potentials and limitations of existing gastroretentive drug delivery systems used in cancer chemotherapy. Due to increased stomach retention and modified drug release properties, gastroretentive controlled drug delivery systems improve the therapeutic performance of anti-cancer drugs used to treat stomach cancer. Gastroretentive drug delivery systems appear to be a promising carrier for localized chemotherapy with smaller doses and better patient compliance. However, selection of drug candidates, drugfood interactions and chemotherapy-induced gastric discomfort remain the key characteristics that must be addressed to improve treatment outcomes.

Formulation and Evaluation of Floating Tablets of Pantoprazole

Background: Pantoprazole is a protein pump inhibitor (PPI) used to treat acute duodenal ulcers, acute benign gastric ulcers, gastroesophageal reflux disease (GERD), and as a preventative measure for duodenal ulcer. It has a local effect on the stomach and works by competitively inhibiting the enzyme H+/K+ ATP, which is found in the gastric parietal cells. For acute duodenal ulcers, acute benign gastric ulcers, and gastroesophageal reflux disease (GERD), the usual oral dosage recommendation is 45 mg, and it is taken for 8–12 weeks. 
 Objectives: The preparation of pantoprazole floating tablets was attempted in the current investigation and optimize the formulation using different excipients like Hydroxy ethyl cellulose (HEC), cyclodextrin, sodium bicarbonate, citric acid and microcrystalline cellulose were used in the direct compression method to create pantoprazole floating tablets (250 mg).
 Methods: The direct compression method has been used in the current effort to create floating tablets. The active ingredient, sodium bicarbonate, citric acid, microcrystalline cellulose, and hydroxy ethyl cellulose were sieved through sieve no. 60 and blended uniformly with a mortar and pestle. Using a Rotary tablet punch machine, the powder was compacted into tablets after talc and magnesium stearate were added as lubricants
 Results: Preformulation studies were conducted to select suitable excipients, drug/polymer interactions were validated by the FTIR investigation. The manufactured floating tablets were assessed for hardness, weight fluctuation, thickness, friability, drug content homogeneity, floating lag time, and in vitro dissolution experiment studies was conducted. The results were within the limit and were compared with the marketed formulation.
 Conclusion: According to the observations of the current investigation, a floating pantoprazole tablet increases the stomach residence time and bioavailability, increasing therapeutic efficacy. Formulations F1, F2, F4, F5, F7, and F8 showed good floating, but Formulations F3, and F6 showed moderate floating throughout all 8 formulations. The stability analyses that were done for all the formulations showed that the F7 and F8 formulations had good stability.
 Keywords: Pantoprazole, Floating tablet, Hydroxy ethyl cellulose (HEC), Cyclodextrin, In-vitro drug release studies.

Features and Facts of a Gastroretentive Drug Delivery System-A Review.

English oral delivery of drug was the commonly used modality because of patient compliance and ease of administration. After oral administration of any drug, its bioavailability is affected by its residence time in stomach. Recently, gastroretentive drug delivery systems (GRDDS) have gained wide acceptance for drugs with a narrow absorption window, decreased stability at high alkaline pH, and increased solubility at low pH. This approach develops a drug delivery system, which gets retained within gastric fluid, thereby releasing its active principles in the stomach. Some methods used to achieve gastric retention of drugs include the use of effervescence agents, mucoadhesive polymers, magnetic material, bouncy enhancing excipient, and techniques that form plug-like devices that resist gastric emptying. This review provides a concise account of various attributes of recently developed approaches for GRDDS.

Design and Evaluation of Losartan Potassium Effervescent Floating Matrix Tablets: In Vivo X-ray Imaging and Pharmacokinetic Studies in Albino Rabbits.

Losartan potassium (LP) is an angiotensin receptor blocker used to treat hypertension. At higher pH, it shows poor aqueous solubility, which leads to poor bioavailability and lowers its therapeutic effectiveness. The main aim of this research was to develop a direct compressed effervescent floating matrix tablet (EFMT) of LP using hydroxyl propyl methylcellulose 90SH 15,000 (HPMC-90SH 15,000), karaya gum (KG), and an effervescent agent, such as sodium bicarbonate (SB). Therefore, an EFMT has been developed to prolong the stomach residence time (GRT) of a drug to several hours and improve its bioavailability in the stomach region. The blended powder was evaluated for pre-compression characteristics, followed by post-compression characteristics, in vitro floating, water uptake studies, and in vitro studies. The optimized formulation of EFMT was investigated for in vivo buoyancy by X-ray imaging and pharmacokinetic studies in Albino rabbits. The results revealed that the parameters of pre- and post-compression were within the USP limits. All tablets showed good floating capabilities (short floating lag time <1 min and floated for >24 h), good swelling characteristics, and controlled release for over 24 h. The Fourier-transform infrared (FTIR) and differential scanning calorimetry (DSC) spectra showed drug–polymer compatibility. The optimized formulation F3 (HPMC-90SH 15,000-KG) exhibited non-Fickian diffusion and showed 100% drug release at the end of 24 h. In addition, with the optimized formulation F3, we observed that the EFMT floated continuously in the rabbit’s stomach area; thus, the GRT could be extended to more than 12 h. The pharmacokinetic profiling in Albino rabbits revealed that the relative bioavailability of the optimized LP-EFMT was enhanced compared to an oral solution of LP. We conclude that this a potential method for improving the oral bioavailability of LP to treat hypertension effectively.

Formulation & assessment of combined antibiotics in a floating oblong tablet for treatment of H. pylori: (A) Radiological imaging to prove the floating of a high-weight oblong tablet

The floating drug delivery system (FDDS) is considered as a renewable technique in the pharmaceutical technology because the dreams of increasing the stomach residence time for local or systemic effect are continuously actual for different purposes. It was studied for small weight tablet, but it is not clearly studied for the high weight tablet which may be essential for high dose drugs or when combined drugs are needed. Sodium bicarbonate was only used as a gas generating agent to give the chance to increase the weight of the drugs. Factorial experimental design was utilized to statistically analyze factors affecting tablet buoyancy. The results showed that, all factors studied and their interactions have significant effect on the buoyancy lag time. The addition method of gas generating agent has the most significant effect on the buoyancy process regardless of concentration of sodium bicarbonate used. That is due to the gas generation process is an in-organic interaction between the moieties of strong acid normally present in the stomach and the base added to the tablet during formulation. F4 is selected as an optimum formula that achieves the lowest floating lag time (7 s) through intragranular addition of gas generating agent at the highest concentration for in-vivo radiological imaging. In-vivo study in mature human gastrointestinal tract shows that the gastric residence time has extended to 4 h after swallowing the optimum floated high weight tablet at 2 h after meal. Therefore, it is advisable that, such tablet formula should be administered after standard calorific meal since such meal delays the stomach evacuation.

Folate targeted PEGylated liposomes for the oral delivery of insulin: In vitro and in vivo studies

In this study using phospholipids with high transition temperature and taking advantage of PEGylation, we designed liposomal formulation targeted with folic acid (FA) to improve the stability of liposomes with high penetration efficiency at the same time. The results of characterization demonstrated that liposomal formulations are in range of 150−210 nm size with negative surface charge. The results of cell uptake indicated that FA conjugation resulted in the more uptake of insulin. However, the results of transepithelial electrical resistance (TEER) showed no statistical differences among the formulations. The results of biodistribution also demonstrated that PEGylated liposome targeted with FA had more residence time in stomach and intestine along with higher amounts in blood and liver. The anti-diabetic effects of formulation in vivo indicated the efficacy of PEGylated liposome targeted with FA had promising results in decreasing blood glucose and increasing insulin levels. The results of this study indicated that using phospholipids with high Tm along with PEGylation and using targeting ligand could improve efficiency of oral delivery of liposomes which merit further investigation.

Developement and Characterization of Floating Tablets of Nizatidine for Peptic Ulcer

The objective of the present research work is to develop an ideal floating drug delivery system of nizatidine to increase the gastric residence time in stomach. To overcome the short half life and lower bioavailability of drug in tablet form we developed the drug in the form of effervescent floating tablet containing HPMC K100 and sodium bicarbonate by direct compression methodology. The prepared effervescent floating tablets were characterized by thickness, weight variation, hardness, friability, drug content uniformity, in vitro buoyancy time, swelling test, in vitro study and stability study and found that all formulations showed satisfactory results with enhanced half life and bioavailability that is among all formulations F1 formulation exhibited good drug release of 95.03% &amp; has shown floating lag time 55 sec. Finally, it was concluded that formulations of nizatidine floating tablet were successfully prepared and found prolonged drug release for 12 hours thereby getting enhanced bioavailability, patient compliance by reducing dose frequency and gastric residence time.

Gastroretentive drug delivery system: A systematic review

Gastroretentive drug delivery system is a novel drug delivery system that has an upper hand due to its ability to maintain prolonged stomach retention and thereby increase the stomach residence time of drugs and also enhance the bioavailability of drugs. Oral sustained drug delivery system is complicated by reduced stomach residence time (GRTs) and erratic stomach emptying time etc. In order to overcome these limitations, various approaches have been proposed to increase the gastric residence of drug delivery systems in the upper part of the gastrointestinal tract peptic ulcer, stomach ulcer, or gastric ulcer, also known as peptic ulcer disease, is a very common chronic stomach disorder that is mainly caused by stomach lining damage. Various factors such as pepsin, gastric acid, H. Pylori, NSAIDs, prostaglandins, mucus, bicarbonate, and mucosal blood flow play an important role in the development of peptic ulcers and so on. In this review article we concentrate on some important mechanisms for the delivery of gastro-retentive drugs (GRDDS) (floating, bioadhesive, high density, swellable, raft forming, and magnetic systems) which will be useful in the treatment of peptic ulcer in different dosage types. This manuscript highlights various developmental approaches, Comparison between Conventional drug delivery systems and Gastro retentive Drug delivery systems, characterization aspects, potential drug candidates, unsuitable drug candidates, List of commercialized gastro-retentive drug delivery system, advantages and applications of gastroretentive systems.

Contemporary Development in Floating Oral In-Situ Gel: A Review

Conventional oral dosage forms having low bioavailability problems due to their rapid gastric transition from stomach, in case of drugs which are less soluble at alkaline pH of intestine. Further drugs which produce their nearby activity in stomach, get quickly emptied don't get enough residence time in stomach. To avoid these problems, different endeavors have been made to draw out the the retention time of drug in stomach. The development of in situ gel systems has gotten impressive consideration in the course of recent years as it gives the most ideal approach to conquer problems of immediate release and short GI residence of fluids. In situ gel forming drug delivery systems are principle, capable of releasing drug in a sustained manner maintaining relatively constant plasma profiles. The in situ gel dosage form is a liquid before administration and after it interacts with gastric contents gets changed over to gel which floats on gastric contents. In situ gel formation happens because of one or combination of various stimuli like pH change, temperature modulation and ionic crosslinking. This accomplishes expanded residence as well as sustained release. It can be easily applied to the site of drug absorption where they swell to form a strong gel that is capable of prolonging the residence time of the active substance. This review gives a short thought regarding floating oral in situ gel formation and research done by different researchers on various drugs.

Development of Novel High Density Gastroretentive Multiparticulate Pulsatile Tablet of Clopidogrel Bisulfate Using Quality by Design Approach.

Myocardial infarction, i.e., heart attack, is a fatal condition which is on the increase all over the world. It is reported that a large number of heart attack occur in morning hours which are attributable to platelet aggregation. Chronotherapy at this stage can be crucial. Clopidogrel bisulfate (CLB) is an antiplatelet agent and has become a drug of choice for prevention of heart attack. It is soluble in acidic pH and has a narrow absorption window. So, its long residence time in stomach is desirable. Therefore, a novel high density tablet was developed comprising multiparticulate pellets with pulsatile release necessary to maintain chronotherapy of heart attack. The pellets were prepared by extrusion-spheronization and coated in fluidized bed processor with different coating material to achieve pulsatile release. The size, shape of pellets, and drug release were evaluated. High density tablet containing coated pellets was formulated and evaluated for retention in stomach. Quality by design tools was used to design and optimize the processes. Timed release observed by dissolution study showed lag time of 6h followed by burst release of drug up to 94% in 1h. Density of tablets was found to be 2.2gcm-3 which is more than gastric fluid. In vivo x-ray studies in rabbit revealed 8h of gastric retention of tablet at the bottom of the stomach. Thus, CLB high density pulsatile system looks to open up a window of opportunity for developing formulations with drugs that are stable in gastric region and needed chronotheraupetic activity.

FORMULATION AND EVALUATION OF GASTRORETENTIVE MICROBALLOONS OF ACEBROPHYLLINE FOR THE TREATMENT OF BRONCHIAL ASTHMA

ABSTRACTObjective: Gastroretentive dosage forms are an approach for prolonged and predictable drug delivery in the upper gastrointestinal tract to controlthe gastric residence time. Microballoons are considered as one of the most promising buoyant drug delivery systems as they possess the advantagesof both multiple-unit systems and good floating properties. Acebrophylline is a xanthine derivative with potent bronchodilator, mucosecretolytic, andanti-inflammatory property. It is used to treat bronchial asthma and chronic obstructive pulmonary diseases.Methods: Microballoons of acebrophylline were prepared by emulsion solvent diffusion method using hydroxypropyl methylcellulose (HPMC) andethyl cellulose (EC) as polymer. The microballoons were evaluated with their micromeritic properties, particle size, tapped density, compressibilityindex, angle of repose, percentage yield, in vitro buoyancy, entrapment efficiency, drug-polymer compatibility, scanning electron microscopy (SEM),and drug release kinetics.Results: The mean particle size of the microballoons formulation MB1 to MB6 containing HPMC and EC was in the range between 226±16 and 577±10,respectively. The mean particle size of microballoons was found to increase with increasing polymer concentration. The micromeritic properties werefound be good, and SEM confirmed their hollow structure with smooth and dense which helped to prolong floating to increase residence time instomach. The in vitro drug release studies showed controlled release of acebrophylline microballoons in the simulated gastric fluid more than 12 hrs.Conclusions: The results showed that the prepared floating microballoons of acebrophylline prove to be potential multiple-unit delivery devicesadaptable for safe and effective sustained drug delivery.Keywords: Microballoons, Acebrophylline, Bronchial asthma, Hydroxypropyl methylcellulose, Ethyl cellulose.

DEVELOPMENT OF MUCOADHESIVE MICROSPHERES OF LEVOFLOXACIN FOR THE TREATMENT OF H. PYLORI INFECTION

The rationale of the present investigation is to develop a new oral drug delivery system utilizing both the concepts of controlled release and mucoadhesiveness, which could remain in stomach and control the drug release for longer period of time and thus to improve the bioavailability of the drug and reducing its dose related side effects. Gelatin/Acrypol 934P mucoadhesive microspheres of Levofloxacin were prepared by Emulsification cross- linking method. Drug and excipients interactions are tested using Fourier Transform-Infrared Spectroscopy, indicated no interactions. The average particle size for optimized formulations of Gelatin/Acrypol 934P microspheres were found to be 41.5µm. Photomicrographs revealed that the microspheres were spherical in shape. The drug entrapment efficiency for Gelatin/ Acrypol 934P microspheres was found to be 85.43%. In vitro drug release from Gelatin/ Acrypol microspheres showed more than 75% of the drug was released within 8 Hr, while pure drug showed complete drug release within 3 hours. This suggested controlled delivery of Levofloxacin for a longer period. Regression analysis revealed that the drug release from the microspheres was followed zero order kinetics. SEM images suggested spherical shape with smooth surface of microspheres formulations. Optimized formulation of Gelatin/ Acrypol 934P microspheres showed excellent mucoadhesivity i.e., 86.5%. Thus, the proposed Gelatin/ Acrypol 934P mucoadhesive microspheres might make a contribution in complete eradication of Helicobacter pylori owing to prolonged stomach residence time and small particle size.

Long-term stability study of Prussian blue—A quality assessment of water content and cyanide release

Context. Prussian blue, ferric hexacyanoferrate is approved for (oral) treatment of internal contamination with radioisotopes of cesium or thallium. Cyanide makes up 35–40% of Prussian blue's molecular composition; thus, cyanide may be released during transit through the digestive tract under physiological pH conditions. Objectives. The purpose of this study is to assess the long-term stability of Prussian blue drug products and active pharmaceutical ingredients and its impact on cyanide release. The study involves the determination and comparison of the loss in water content and cyanide released from Prussian blue under pH conditions that bracket human physiological exposure. Methods. Test samples of active pharmaceutical ingredient and drug product were stored for 10 years at ambient temperatures that mimic warehouse storage conditions. Water loss from Prussian blue was measured using thermogravimetric analysis. An in vitro physiological pH model that brackets gastric exposure and gastrointestinal transit was utilized for cyanide release. Prussian blue was incubated in situ at pH: 1.0, 5.0, and 7.0 @ 37°C for 1–24 h. Cyanide was measured using a validated colorimetric method by UV–Vis spectroscopy. Results. Although the water content (quality attribute) of Prussian blue active pharmaceutical ingredient and drug product decreased by about 10.5% and 13.8%, respectively, since 2003, the cyanide release remained comparable. At pH of 7.0 for 24 h cyanide released from active pharmaceutical ingredient-1 was 21.33 ± 1.76 μg/g in 2004, and 28.45 ± 3.15 μg/g in 2013; cyanide released from drug product-1 was 21.89 ± 0.56 μg/g in 2004, and 27.31 ± 5.78 μg/g in 2013. At gastric pH of 1.0 and upper gastrointestinal pH of 5.0, the data for active pharmaceutical ingredients and drug products were also comparable in 2013. The cyanide release is still pH-dependent and follows the same trend as observed in 2003 with minimum release at pH of 5.0 and maximal release at pH of 1.0. In summary, this is the long-term stability study of Prussian blue which correlates cyanide release to water loss. Cyanide released from Prussian blue was maximum at pH of 1.0 (47.47 μg/g) and minimum at pH of 5.0–7.0 (20.01 μg/g). Conclusions. Based on maximal dose, maximal residence time in stomach and intestine, the maximal cyanide released from Prussian blue is about 1.31 mg, which is far below the minimal lethal dose of cyanide of 50 mg, and therefore does not present a safety concern following long-term storage.

N Vivo Evaluation of a Gastroretentive Drug Delivery System Based on Enteric-Coated Floating Tablets

Floating dosage forms are supposed to exhibit an enhanced gastric residence time. Their development is challenging as the prediction of the retention potential in humans based on in vitro studies and animal models is difficult. A strategy to determine the stomach residence time of a floating dosage form with an inherently low density in human without using imaging techniques was explored in a self-experiment. Floating tablets and non-floating controls were prepared containing caffeine as a model drug. The compacts had a pH-dependent entericcoating to assess their stomach residence time. Since caffeine is rapidly absorbed in the gastrointestinal tract, the prolonged gastric retention of tablets can be demonstrated by a delayed systemic exposure. Caffeine and paraxanthine were determined in capillary blood by liquid chromatography coupled to tandem mass spectrometry. An increase in caffeine and paraxanthine blood levels was observed in human volunteers after 90 to 180 min for the non-floating controls. For the floating tablets, no elevated blood concentrations were found in two out of three participants during 8 h of sample collection. The results demonstrate the technical feasibility of the proposed clinical study protocol. Follow-up clinical trials will be needed to confirm the preliminary data on stomach residence time of our floating dosage form.

A novel in situ gel formulation of ranitidine for oral sustained delivery.

The main purpose of this study was to develop a novel, in situ gel system for sustained delivery of ranitidine hydrochloride. Ranitidine in situ gels at 0.2%, 0.5%, and 1.0% gellan gum concentration (w/v) were prepared, respectively, and characterized in terms of preparation, viscosity and in vitro release. The viscosity of the gellan gum formulations in solution increased with increasing concentrations of gellan gum. In vitro study showed that the release of ranitidine from these gels was characterized by an initial phase of high release (burst effect) and translated to the second phase of moderate release. Single photon emission computing tomography technique was used to evaluate the stomach residence time of gel containing 99mTc tracer. The animal experiment suggested in situ gel had feasibility of forming gels in stomach and sustained the ranitidine release from the gels over the period of at least 8 h. In conclusion, the in situ gel system is a promising approach for the oral delivery of ranitidine for the therapeutic effects improvement.

Mucoadhesive microparticulate drug delivery system of curcumin against Helicobacter pylori infection: Design, development and optimization

The purpose of the present research was to develop and characterize mucoadhesive microspheres of curcumin for the potential use of treating gastric adenocarcinoma, gastric and duodenal ulcer associated with Helicobacter pylori. Curcumin mucoadhesive microspheres were prepared using ethyl cellulose as a matrix and carbopol 934P as a mucoadhesive polymer by an emulsion-solvent evaporation technique. Response surface methodology was used for optimization of formulation using central composite design (CCD) for two factors at three levels each was employed to study the effect of independent variables, drug:polymer:polymer ratio (curcumin:ethylcellulose:carbopol 934P)(X1) and surfactant concentration (X2) on dependent variables, namely drug entrapment efficiency (DEE), percentage mucoadhesion (PM), in vitro drug release and particle size (PS). Optimized formulation was obtained using desirability approach of numerical optimization. The experimental values of DEE, PM, % release and PS after 8 h for the optimized formulation were found to be 50.256 ± 1.38%, 66.23%±0.06, 73.564 ± 1.32%, and 139.881 ± 2.56 μm, respectively, which were in close agreement with those predicted by the mathematical models. The drug release was also found to be slow and extended more than 8 h and release rates were fitted to the Power law equation and Higuchi model to compute the diffusional parameters. The prolonged stomach residence time of curcumin mucoadhesive microspheres might make a contribution to H. pylori complete eradication in combination with other antimicrobial agents.

Encapsulation of Rifampicin in a solid lipid nanoparticulate system to limit its degradation and interaction with Isoniazid at acidic pH

Rifampicin (RIF), a vital constituent of antitubercular therapy, hydrolyzes at the acidic pH of the stomach. The degradation is further enhanced by its interaction with Isoniazid (INH). Extent of RIF decomposition, in the presence and absence of INH, was determined at pH 1.2 (pH of empty stomach) at 37°C for 4 h (maximum stomach residence time). Both the drugs decomposed at gastric pH (26.5% and 1.43% for RIF and INH respectively). Considering that solid lipid nanoparticles (SLNs) avert drug-drug interaction and also drug degradation, we incorporated RIF into SLNs. Latter reduced its degradation to ~9% (from 26.50% when present alone) and to ~20% (from 48.81% when INH was also present). Subsequent to this, we also incorporated INH into SLNs and the percent degradation of RIF in this combination (RIF SLNs+INH SLNs) further reduced to 12.35%. Furthermore, the degradation of INH in combination with RIF also reduced significantly from 13.2% to 2.7% when both the drugs were encapsulated individually within SLNs. Study therefore highlights the need to develop combinations of antitubercular drugs (ATDs) with caution and also establishes the usefulness of nanoparticulate technology to avoid drug-drug interaction.