Physiologically active hydrogel (in situ gel) of sparfloxacin and its evaluation for ocular retention using gamma scintigraphy.

OBJECTIVE: Due to the structure and physiological barrier of eye, only 1% of instilled dose is available for action on the corneal surface. In this work, we developed and evaluated chitosan (pH sensitive) and gellan gum (ion sensitive) in situ gel of sparfloxacin to improve precorneal residence time. MATERIALS AND METHODS: A protocol for radiolabeling of sparfloxacin with Tc-99m was optimized to study the ocular retention using gamma scintigraphy technique. RESULTS: The clear formulation was developed. In vitro release showed a sustained and prolonged release compared to plain eye drop solution. Dynamic and static gamma scintigraphy showed better retention than plain eye drops. The ocular tolerance test (hen's egg test-chorioallantoic membrane test and infra-red study) showed that the formulation is nonirritant and can be used as ocular vehicle. CONCLUSION: Radiolabel protocol for sparfloxacin was successfully developed and evaluated on ocular retention studies of developed in situ gel. The developed in situ gel is non irritant and can go further with clinical evaluation.

Current scenario of spurious and substandard medicines in India: a systematic review.

Globally, every country is the victim of substandard or spurious drugs, which result in life threatening issues, financial loss of consumer and manufacturer and loss in trust on health system. The aim of this enumerative review was to probe the extent on poor quality drugs with their consequences on public health and the preventive measures taken by the Indian pharmaceutical regulatory system. Government and non-government studies, literature and news were gathered from journals and authentic websites. All data from 2000 to 2013 were compiled and interpreted to reveal the real story of poor quality drugs in India. For minimizing spurious/falsely-labelled/falsified/counterfeit drugs or not of standard quality drugs, there is urgent requirement of more stringent regulation and legal action against the problem. However, India has taken some preventive steps in the country to fight against the poor quality drugs for protecting and promoting the public health.

An alternative in situ gel-formulation of levofloxacin eye drops for prolong ocular retention.

INTRODUCTION: Delivering drugs to ocular region is a challenging task. Eye physiological barriers lead to relatively less therapeutic and bioavailability effect by the conventional eye drops. This may be overcome by the use of in situ gel delivery system. OBJECTIVE: The objective of our work was to formulate an ocular delivery system of levofloxacin, based on the concept of ion (sodium alginate) and pH (chitosan) activated in situ gelation concept. Due to its elastic properties, in situ gels resist the ocular drainage of drug leading to longer contact times with ocular surface. MATERIALS AND METHODS: The formulation was evaluated for physicochemical characteristics, in vitro drug release. Ocular retention studies were carried out by Gamma scintigraphy. Time activity curve was plotted between marketed formulation and developed formulation for comparing drug drainage from the eye with time. Ocular tolerance test was performed by handheld infra-red camera. RESULTS AND DISCUSSION: The formulations showed a first-order release pattern over 12 h. Both in vitro release studies and in vivo gamma scintigraphy precorneal retention studies indicated better therapeutic efficacy compared with standard eye drops. CONCLUSION: The results demonstrated that the developed in situ gel of levofloxacin is nonirritant, has prolonged action and is a better option in terms of retention, ocular bioavailability and patient compliance when compared with plain eye drops formulation.

Nanoparticles laden in situ gel of levofloxacin for enhanced ocular retention.

Availability of proper concentration of medicament on to the corneal surface is a challenging task. Many novel formulations, i.e. hydrogels, nanoparticles, ocuserts, etc. had been tested to improve ocular bioavailability, out of which our group found, in situ gel and polymeric nanoparticle are the most interesting approach to achieve ocular retention. We found that in situ gel stay only for 12 h and poly(lactic-co-glycolic acid (PLGA) nanoparticles are non mucoadhesive in nature so we try to combine both these formulations and termed it as "Nanoparticle laden in situ gel". Here we prepare nanoparticle laden in situ gel containing levofloxacin encapsulated PLGA nanoparticle, incorporated in chitosan in situ gel and evaluated its ocular retention by gamma scintigraphy in rabbits. The observations of acquired gamma camera images showed good retention over the entire precorneal area. From static and dynamic gamma scintigraphy evaluation, we can be interpret that developed nanoparticle laden in situ gel formulation cleared at a very slow rate and remained at corneal surface for longer duration than marketed formulation, in situ gel and nanosuspension alone.

Validated HPLC method for the simultaneous determination of taxol and ellagic acid in a Punica granatum fruit extract containing combination formulation.

A simple, rapid, precise and accurate isocratic reversed-phase high performance liquid chromatography (HPLC) method was developed and validated for the simultaneous determination of paclitaxel and ellagic acid in a combination nanoformulation. Separation was achieved using a 25 x 4.6 mm column, particle size 5 microm C18 reverse phase column (Luna), with a mobile phase consisting of methanol and 0.05% H3PO4, in gradient elution mode with a mobile phase flow rate of 1 mL/min, using UV visible detection at 230 nm. Sharp and well defined peaks were obtained at retention times of 13.75 min. and 11.6 min. for paclitaxel and ellagic acid, respectively. Regression analysis showed a good linear relationship (r2 = 0.996 +/- 0.0011) and (r2 = 0.993 +/- 0.0011) over wide ranges of 5-500 microg/ml and 1-500 microg/ml for paclitaxel and ellagic acid, respectively. LOD and LOQ of paclitaxel were 30 ng/ml and 100 ng/ml, respectively, while for ellagic acid LOD and LOQ were 300 ng/ml and 1 microg/ml, respectively. The accuracy of the method was determined by recovery studies using the standard addition method and was found to be in the range of 99.61-101.21% and 98.70-102.22% for paclitaxel and ellagic acid, respectively. The relative standard deviation (% RSD) for precision, repeatability and robustness was less than 2%. The ellagic acid content in fruits of Punica granatum and combination formulation with paclitaxel was analyzed and found to be 0.04% w/w and 0.0012%w/w, respectively. The proposed, developed and validated HPLC method for the simultaneous quantification of ellagic acid and paclitaxel can be used for the quality control and standardization of several crude drugs and different combination formulations, in which ellagic acid is present.

Development, characterization and in vitro assessement of stearylamine-based lipid nanoparticles of paclitaxel.

The objective of the study was to design and evaluate a solid lipid nanoparticle (SLN) drug delivery system for delivery of paclitaxel. Components of the SLN were lipid (stearylamine) and surfactants (Pluronic F68 and Soya lecithin). The paclitaxel loaded nanoparticles were prepared by a modified solvent injection method. Experiments were carried out with excipients, where surfactants, lipid and drug molar ratios were varied to optimize the formulation characteristics. The in vitro drug release profile from the nanoparticles followed a diffusion controlled mechanism. The modified solvent injection method ensured high entrapment efficiency (approximately 75%), produced smaller, stable nanoparticles with a narrow size distribution and proved to be a reproducible and fast production method. The present study describes the feasibility and suitability of stearylamine based SLN produced using a mixture of surfactants to develop a clinically useful system with targeting potential for poorly soluble antineoplastic drugs.

Development and performance evaluation of alginate-capped amphotericin B lipid nanoconstructs against visceral leishmaniasis.

The present study was aimed to assess the improvement of existing treatment regimens of Amphotericin B nanoconstrcuts which synergises with alginate for immunostimulation against visceral leishmaniasis. The particle size of Lip-nano (Plain AmB nanoconstructs) and Alg-Lip-nano (alginate capped Lip-nano) was 108.3 +/- 4.3 and 134.2 +/- 5.1 while zeta potential was (+) 28.4 +/- 3.3 and (-) 19.8 +/- 2.1 respectively. Percentage of parasite inhibition (intramacrophagic amastigotes) at 0.1 microg/ml conc. of AmB in case of Alg-Lip-nano (58%) was significantly higher (P = 0.05) compared to Lip-nano (48%). This supports that alginate coating over particles can activate macrophages to synergistically act with AmB in effective killing of parasite. This observation generates interest that immunotherapy with chemotherapeutic activity of AmB can effectively increase cure rate in visceral leishmaniasis.

Novel polymer coupled lipid nanoparticle of paclitaxel with synergistic enhanced efficacy against cancer.

This study was aimed to develop chitosan coupled lipid nanoparticle (Ch-Ptx-Lip), where immunomodulatory activity of chitosan and chemotherapeutic effect of paclitaxel can synergistically enhance efficacy of this novel drug delivery system. Particle size, zeta potential and % Entrapment Efficiency (%EE) of Ch-Ptx-Lip was found to be 113.3 +/- 4.5 nm (PDI: 0.38), (+)35.7 +/- 2.9 mV and 96.4 +/- 1.8% respectively. Morphological evaluation of these particles by TEM shows circular bilayer structure along with outer polymer layers. Ch-Ptx-Lip showed significantly enhanced cytotoxicity (p < 0.05) compared with marketed formulation (Ptx Solution) and Ptx-Lip when evaluated in-vitro by MTT assay on MCF-7 cell lines. Improved efficacy with lower dose of drug can be a new strategy against cancer with minimum side effects and shorter treatment duration.

Biodegradable levofloxacin nanoparticles for sustained ocular drug delivery.

Drug delivery to ocular region is a challenging task. Only 1-2% of drug is available in eye for therapeutic action, rest of the drug is drained out through nasolachrymal drainage system and other ocular physiological barriers. To overcome these problems of conventional dosage form, novel drug delivery systems are explored like nanoparticles. In our present work, levofloxacin encapsulated poly(lactic-co-glycolic acid) nanoparticles were developed and evaluated for various parameters like particle size, ζ potential, in vitro drug release and ex vivo transcorneal permeation. Microbiological efficacy was tested against Staphylococcus aureus using cup-plate method. Precorneal residence time was studied on albino rabbits by γ scintigraphy after radiolabeling of levofloxacin by Tc-99m. Ocular tolerance was evaluated using hen's egg chorioallantoic membrane (HET-CAM) test. The developed nanoparticles were of spherical shape with a mean particle size of 190-195 nm with a ζ potential of -25 mV. The drug entrapment efficiency was found to be near 85%. In vitro drug release profile shows initial burst release followed by extended release up to 24 h. Microbiological assay showed equivalent zone of inhibition compared to marketed formulation. γ Scintigraphy images of developed formulation, suggested a good spread and good retention over precorneal area. The nanosuspension thus developed was retained for the longer time and drained out from the eye very slowly compared to marketed formulation as significant radioactivity was recorded in later in kidney and bladder. The developed nanosuspension with a mean score of 0.33 up to 24 h in HET-CAM assay, showed the nonirritant efficacy of developed formulation. The stability studies yielded a degradation constant less then 5 × 10(-4), proving a stable formulation with an arbitrary shelf life of 2 years.

A single reversed-phase UPLC method for quantification of levofloxacin in aqueous humour and pharmaceutical dosage forms.

An attempt was made to develop a single, rapid, specific, and sensitive gradient reversed-phase ultra-performance liquid chromatographic method for quantitative analysis of levofloxacin. The single method thus developed is applied for the quantification of levofloxacin both in aqueous humour as well as pharmaceutical dosage forms (i.e., tablets and eye drops). The newly developed method is applicable for pharmacokinetic studies of eye formulations. The chromatographic separation of levofloxacin was achieved on a Waters Acquity HSS T-3 column (100 x 2.1 mm, 1.8 microm) within a short run-time of 5 min. The method was validated according to the ICH guidelines with respect to system suitability, linearity, limit of quantitation and detection, precision, accuracy, robustness, and specificity. Forced degradation studies were also performed in levofloxacin bulk drug samples to demonstrate the stability-indicating power of the developed ultra-performance liquid chromatography method. The developed method was then successfully applied for the ocular pharmacokinetic study of levofloxacin eye formulations and assay of levofloxacin pharmaceutical dosage form.

Development and validation of a stability-indicating RP-UPLC method for the quantitative analysis of sparfloxacin.

A rapid, specific, and sensitive ultra-performance liquid chromatographic (UPLC) method for quantitative analysis of sparfloxacin in bulk drug and pharmaceutical formulations has been developed and validated. In this work, a new gradient reversed-phase chromatographic method was developed. The newly developed method is applicable for assay determination of the active pharmaceutical ingredient. The chromatographic separation of sparfloxacin was achieved on a Waters Acquity HSS T-3 column (100 x 2.1 mm, 1.8 microm) within a short runtime of 5 min. The method was validated according to the ICH guidelines with respect to system suitability, linearity, limit of quantitation and detection, precision, accuracy, robustness, and specificity. Forced degradation studies were also performed for sparfloxacin bulk drug samples to demonstrate the stability indicating power of the UPLC method. Comparison of system performance with conventional HPLC was made with respect to analysis time, efficiency, and sensitivity. The developed method was applied for the assay of marketed sparfloxacin formulations like tablets and eye drops.

Nano-vectors for the Ocular Delivery of Nucleic Acid-based Therapeutics.

Nucleic acid-based therapeutics have gained a lot of interest for the treatment of diverse ophthalmic pathologies. The first to enter in clinic has been an oligonucleotide, Vitravene(®) for the treatment of cytomegalovirus infection. More recently, research on aptamers for the treatment of age related macular degeneration has led to the development of Macugen(®). Despite intense potential, effective ocular delivery of nucleic acids is a major challenge since therapeutic targets for nucleic acid-based drugs are mainly located in the posterior eye segment, requiring repeated invasive administration. Of late, nanotechnology-based nano-vectors have been developed in order to overcome the drawbacks of viral and other non-viral vectors. The diversity of nano-vectors allows for ease of use, flexibility in application, low-cost of production, higher transfection efficiency and enhanced genomic safety. Using nano-vector strategies, nucleic acids can be delivered either encapsulated or complexed with cationic lipids, polymers or peptides forming sustained release systems, which can be tailored according to the ocular tissue being targeted. The present review focuses on developments and advances in various nano-vectors for the ocular delivery of nucleic acid-based therapeutics, the barriers that such delivery systems face and methods to overcome them.

Development and evaluation of buccal bioadhesive tablet of an anti-emetic agent ondansetron.

The aim of the present study was to develop and evaluate a buccal adhesive tablet containing ondansetron hydrochloride (OH). Special punches and dies were fabricated and used while preparing buccal adhesive tablets. The tablets were prepared using carbopol (CP 934), sodium alginate, sodium carboxymethylcellulose low viscosity (SCMC LV), and hydroxypropylmethylcellulose (HPMC 15cps) as mucoadhsive polymers to impart mucoadhesion and ethyl cellulose to act as an impermeable backing layer. The formulations were prepared by direct compression and characterized by different parameters such as weight uniformity, content uniformity, thickness, hardness, swelling index, in vitro drug release studies, mucoadhesive strength, and ex vivo permeation study. As compared with the optimized formulation composed of OH--5 mg, CP 934--30 mg, SCMC LV--165 mg, PEG 6000--40 mg, lactose--5 mg, magnesium stearate--1.5 mg, and aspartame--2 mg, which gave the maximum release (88.15%), non-bitter (OH) that form namely ondansetron base and complexed ondansetron was used in order to make the selected formulation acceptable to human. The result of the in vitro release studies and permeation studies through bovine buccal mucosa revealed that complexed ondansetron gave the maximum release and permeation. The stability of drug in the optimized adhesive tablet was tested for 6 h in natural human saliva; both the drug and device were found to be stable in natural human saliva. Thus, buccal adhesive tablet of ondansetron could be an alternative route to bypass the hepatic first-pass metabolism and to improve the bioavailability of (OH).

Characterization and in vitro assessment of paclitaxel loaded lipid nanoparticles formulated using modified solvent injection technique.

This study investigates the design and characterization of solid lipid nanoparticles (SLNs) containing paclitaxel fabricated by a modified solvent injection technique using stearic acid as lipid and stabilized by a mixture of surfactants, for future evaluation of this colloidal carrier system for the oral delivery of paclitaxel, devoid of the side effects of Cremophor EL. SLN formulations of paclitaxel stabilized by mixture of surfactants i.e. lecithin/poloxamer 188 were developed with smaller size and narrow size distribution. The paclitaxel-loaded SLNs exhibited spherical shape with smooth surface as analyzed by transmission electron microscopy (TEM). The average particle size obtained through this method was found to be approximately 113 nm. The zeta potential was between -32 and -39 mV with poloxamer 188. Encapsulation efficiencies of about 72.18 +/- 3.7 and 89.0 +/- 2.4% were achieved using 0.05 and 0.25 mmol of paclitaxel, respectively. Paclitaxel showed a sustained in vitro release profile and was found to follow Higuchi kinetic equations. In vitro cytotoxicity assay confirmed that paclitxel entrapped in SLNs showed higher cytotoxicity against cultured hepatocelluler carcinoma cells than paclitaxel alone. The modified solvent injection technique used in this research proved to be a simple, easily available and effective method to produce SLNs and could be used for controlled delivery of different lipophilic drugs for cancer chemotherapy.

Development and characterization of 99mTc-timolol maleate for evaluating efficacy of in situ ocular drug delivery system.

In situ gel-forming systems have drawn much attention of current researchers to overcome the poor bioavailability from the conventional eye drops. The present work described formulation and pharmacoscintigraphic evaluation of timolol-maleate-loaded chitosan/hydroxy propyl methyl cellulose (HPMC)-based polymer matrix for enhanced ocular retention. Chitosan and HPMC ratio was optimized and formulation was characterized for various in vitro parameters. The ocular retention was studied on New Zealand rabbits by gamma scintigraphy, which is a very simple and noninvasive technique. For scintigraphy study, the drug timolol maleate was radiolabeled (99m)Tc by direct labeling method using SnCl(2).2H(2)O as reducing agent. The labeling procedure was optimized to get maximum labeling efficiency (>98%). In vitro stability of the radiolabeled drug ((99m)Tc-timolol maleate complex) was checked and it was found to be stable for up to 24 h. Plain drug eliminates rapidly as significant activity was recorded in kidney and bladder after 2 h of ocular administration. It was evident from the scintigraphic images and the time-activity curve plotted from the data that the plain drug solution cleared very rapidly from the corneal region and reached into systemic circulation via nasolachrymal drainage system, as significant activity was recorded in kidney and bladder after 2 h of ocular administration. Developed formulation cleared at a slow rate and remained at corneal surface for longer time duration. No radioactivity was observed in systemic circulation after 2 h. Ocular irritation of the developed formulation was also checked by hen's egg chorioallantoic membrane test and formulation was found to be practically nonirritant. The study signified the potential of gamma scintigraphy in evaluation of novel drug delivery systems in a noninvasive manner.

Optimization of chitosan succinate and chitosan phthalate microspheres for oral delivery of insulin using response surface methodology.

In the present study, a Box-Behnken experimental design was employed to statistically optimize the formulation parameters of chitosan phthalate and chitosan succinate microspheres preparation. These microspheres can be useful for oral insulin delivery system. The effects of three parameters namely polymer concentration, stirring speed and cross linking agent were studied. The fitted mathematical model allowed us to plot response surfaces curves and to determine optimal preparation conditions. Results clearly indicated that the crosslinking agent was the main factor influencing the insulin loading and releasing. The in vitro results indicated that chitosan succinate microspheres need high amount of crosslinking agent to control initial burst release compared to chitosan phthalate microspheres. The reason may be attributed that chitosan succinate is more hydrophilic than chitosan phthalate. The relative pharmacological efficacy for chitosan phthalate and chitosan succinate microspheres (18.66 +/- 3.84%, 16.24 +/- 4%) was almost three-fold higher than the efficacy of the oral insulin administration (4.68 +/- 1.52%). These findings suggest that these microspheres are promising carrier for oral insulin delivery system.

Techniques to develop and characterize nanosized formulation for salbutamol sulfate.

The present study relates to enhancing the dosing efficiency of pharmaceutical dry powder formulations administered by pulmonary inhalation. In particular, the study relates to the provision of dry powder inhalers (DPI) by forming nanosized particles of salbutamol sulfate (SBM) in order to augment the drug penetrability and deposition in the lungs. SBM, an antiasthmatic was selected to be developed into a nanosized formulation by different techniques like solvation, high-pressure homogenization, and spray drying, which were then compared on the basis of particle shape, particle size, and particle size distribution. In case of solvation method the nanosuspension was prepared by dispersing SBM into a nonsolvent and adding Tween-80 as a surfactant to prevent the agglomeration, the particles obtained therein were in the range of 2-10 mu. The second attempt was made by passing the suspension of SBM through high-pressure homogenizer at 10,000-15,000 psi. A treatment of six cycles of homogenization in presence of a Tween-80 as surfactant was found to give a nanosuspension within a size range 50-100 nm. The only drawback seemed with this technique was the low-product yield and high-processing time (3-4 h). In order to overcome this drawback spray-drying technique was further explored; the solution of SBM containing Tween-80 was stirred on magnetic stirrer at 1,200 rpm and finally dried by using spray dryer at an inlet and outlet temperature of 75 degrees C and 56 degrees C, respectively. The feed rate for spray dryer was kept to be 91 ml/h. The sample was collected and analyzed for particle size distribution which was found to be in the range of 50-100 nm. Keeping in view the positive outcomes in terms of higher yield and lower processing time, the spray-drying technique was taken to give the optimized formulation. Nanosized particles, thus obtained were evaluated for particle size, surface topology and particles size distribution, by Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), and Quasi-elastic light scattering (QELS) technique, respectively. The nanosized particles were subjected to investigate changes on the physical stability of the powder, for this different analytical method was used as: Fourier transform infrared spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD) analysis and thus the result indicates that there was no physical disparity when compared with the commercial SBM sample.

Radiolabeling and evaluation of alginate blend-isoniazid microspheres by 99mTc for the treatment of tuberculosis in rabbit model.

Isoniazid (INH) is the first line anti-tubercular drug that is widely used in the treatment of tuberculosis. (99m)Tc-alginate-INH microsphere scintigraphy has been demonstrated to be a useful noninvasive imaging technique for microsphere deposits located in different organs of the rabbits. The aim of this study was to develop an improved formulation, to validate the formulation for long-time retention, as well as to assess radiotracer stability by novel quality control methods. Our study reports the labeling and evaluation of alginate blends-INH microspheres. The incorporation efficiency of optimized formulation was 89% w/w. The in vitro release study was carried out in simulated intestinal fluid at pH 7.4, and it was found that the formulation delivered the drug for 36 h. The labeling efficiency of (99m)Tc-alginate blends-INH microspheres was seen at various pH (i.e. pH ranging from 5 to 7.5) and different concentration of stannous chloride dehydrate (i.e. 25-200 microg) and it was concluded that 96% labeling efficiency was achieved in case of pH 7.5 and 60 microg stannous chloride. The stability study was carried out in saline and serum and it was found that the complex was highly stable in vitro and in vivo. The blood clearance in rabbits showed bi-exponential pattern depicting that 50% of activity washed out at 2 h with t(1/2(Fast)) was 2.1 h and t(1/2(Slow)) was 12.5 h. Bio-distribution was normal and the experimental mice showed major accumulation of the radiolabeled formulation in liver, intestine, lungs and kidneys, indicating hepatobiliary and renal route of excretion. The distribution of the drugs to the lung was showing its efficiency in the treatment of tuberculosis.

Design and in vitro characterization of buccoadhesive drug delivery system of insulin.

A buccoadhesive drug delivery system of Insulin was prepared by solvent casting technique and characterized in vitro by surface pH, bioadhesive strength, drug release and skin permeation studies. Sodium carboxymethylcellulose-DVP was chosen as the controlled release matrix polymer. The optimized formulation J(4) contained Sodium carboxy methyl cellulose-DVP 2% (w/v), insulin (50 IU/film), propylene glycol (0.25 ml) and Isopropyl alcohol: water (1:4) as solvent system. Bioadhesive strength of the prepared patches was measured on a modified physical balance using bovine cheek pouch as the model membrane. In vitro release studies were carried out at 37 +/- 2 degrees using phosphate buffer pH 6.6, in a modified dissolution apparatus fabricated for the purpose. Cumulative amount of drug released from the optimized formulation J(4) was 91.64% in 6 hours. In vitro permeation studies were carried out on J(4) at 37 +/- 2 degrees using Franz diffusion cell. Cumulative amount of drug permeated from J(4) was 6.63% in 6 hours. In order to enhance the permeation of protein drug, different permeation enhancers were evaluated. The results suggested that sodium deoxycholate 5% (w/v) was the best permeation enhancer among those evaluated. It enhanced the permeation of insulin from 6.63% to 10.38% over a period of 6 hours. The optimized patches were also satisfactory in terms of surface pH and bioadhesive strength. It can also be easily concluded that the system is a success as compared to the conventional formulations with respect to invasiveness, requirement of trained persons for administration and most importantly, the first pass metabolism.

Reconstituted powder for suspension of antitubercular drugs formulated as microspheres for pediatric use.

The aim of the present investigation was to develop a novel dosage form of rifampicin and isoniazid to minimize degradation of rifampicin in acidic medium, to modulate the release of rifampicin in the stomach and isoniazid in the intestine, and to provide pediatric compliance. Rifampicin slowly diffuses out through this hydrogel matrix, thereby sustaining its release (50.08%). The release of isoniazid was thus very low in an acidic environment, i.e. simulated gastric fluid (SGF) pH 1.2 (18.98%), while in simulated intestinal fluid (SIF) pH 7.4 the release was sustained and prolonged (76.98%). Good results were obtained for a period of 36 h in SIF pH 7.4 with isoniazid-alginate microspheres. The drug content was calculated on the basis of the drug entrapment efficiency of the individual microsphere formulation (gelatin, 82.32% and sodium alginate blends, 89.31%). Results revealed that an optimized formulation had a sedimentation volume of 0.4. This optimized formulation was found to be stable. Degradation of isoniazid was faster than that of rifampicin. The degradation rate constant at 25°C was found to be 1.9286 × 10(-4) (day-1), so the formulation was predicted to have a shelf life of 1.518 years.