Oral Controlled Drug Delivery Systems Research Articles

HYDROPHILIC MATRIX TABLETS AS ORAL CONTROLLED DRUG DELIVERY SYSTEMS IN 20TH CENTURY: A REVIEW

Matrix systems are easy to formulate compared to other controlled release dosage forms. The manufacture of matrix tablets involves the direct compression of blend of drug, retardant material and additives to form a tablet in which drug is embedded in a matrix core of the retardant. Alternatively, retardant-drug blends may be granulated prior to compression. Of the three classes of retardant material used to formulate matrix tablets, polymers that form hydrophilic matrices are attracting the attention of pharmaceutical technologists. These polymers include Methyl cellulose (MC), Hydroxy ethyl cellulose (HEC), Hydroxy popyl methyl cellulose (HPMC), Sodium carboxy methyl cellulose (NaCMC), carbomers, chitosan, plant gums etc. The hydrophilic matrix-formers alone or in combination with other excipients form gels in situ on coming in contact with biological fluids which control the drug release. The present review gives a detailed account on the factors to be considered in the design of hydrophilic matrix systems, formulation of hydrophilic matrix tablets, in vitro and in vivo evaluation methods and advances in the design of hydrophilic matrix tablets. This review further focuses on the development of oral controlled drug delivery systems using hydrophilic matrix carriers in 20th century.

A Research Work on Design, Development and In-Vitro Evaluation of Losartan Potassium Loaded Pectinate Microspheres

One of the special and innovative drug delivery strategies is the use of microspheres, which can increase a drug's effectiveness by preventing drug dilution in bodily fluids, allowing drug localization and targeting at a specific site, and maintaining drug concentration between MEC and MTC levels.Microspheres are characterized as roughly spherical, solid particles with sizes between 1 to 1000 μm that are intended to be covered in protective materials such as polymeric or waxy coatings. One of the more innovative methods in the field of oral controlled drug delivery systems is the use of microsphere dosage forms, which target a specific area of the body for a prolonged period of time, allowing for more effective local drug delivery as well as improved systemic drug. The % yield of all the losartan potassium loaded pectinate microsphere formulations (LM1 to LM5) was found within the range from 76.74 ± 3.79 % to 89.06 ± 2.67 %.The % entrapment efficiency and particle size of the prepared losartan potassium loaded pectinate microsphere formulations (LM1 to LM5) was found within the range from 63.68 ± 3.55 % to 84.78 ± 2.27 % and 0.78 ± 0.14 mm to 0.91 ± 0.05 mm respectively. Formulations LM1 to LM5 showed 2.12 % to 12.46 % mucoadhesion up to 6 hours in simulated gastric fluid (pH 1.2, 0.1N HCl) and 74.28 % to 96.04 % mucoadhesion up to 6 hours in simulated intestinal fluid (phosphate buffer, pH 6.8).

Design & Evaluation of Pulsatile Drug Delivery of Diltiazem Hcl

Oral controlled drug delivery systems represent the most popular form of controlled drug delivery systems for the obvious advantages of oral route of drug administration.

The Preparation and In-vitro Evaluation of Sustained Release Capsules of Rivastigmine Tartrate

Rivastigmine tartrate is a cholinesterase inhibitor, used in the treatment of dementia associated with Parkinson’s disease and it is currently available in a capsule form. Hydroxy Propyl Methyl Cellulose (HPMC) is the most important hydrophilic carrier material used for the preparation of oral controlled drug delivery systems due to its high swellability and its significant effect on the release kinetics of an incorporated drug. The present study was designed to prepare sustained release granules of Rivastigmine tartrate by using HPMC as matrix former, Microcrystalline cellulose (MCC) as diluent and Magnesium Stearate as lubricant. Blend of Eudragit co-polymers on different ratio was used to coat the granules. The drug-excipient compatibility studies were carried out by using FT-IR, DSC and XRPD analysis. The results shown that there was no significant interaction between the drug and excipients. Granules were prepared by wet granulation method. The granules were subjected to physico-chemical, drug content and in-vitro drug release studies. The best fit release kinetics was achieved with Higuchi equations followed by first order kinetics from the above results it was concluded that extended release granules of Rivastigmine tartrate can be prepared by using HPMC and also found that coating of granules with Eudragit co-polymers also effective to extend the release of drug.

Cydonia oblonga-Seed-Mucilage-Based pH-Sensitive Graft Copolymer for Controlled Drug Delivery-In Vitro and In Vivo Evaluation.

The primary objective of this study was to assess the potential utility of quince seed mucilage as an excipient within a graft copolymer for the development of an oral-controlled drug delivery system. The Cydonia oblonga-mucilage-based graft copolymer was synthesized via a free radical polymerization method, employing potassium per sulfate (KPS) as the initiator and N, N-methylene bisacrylamide (MBA) as the crosslinker. Various concentrations of monomers, namely acrylic acid (AA) and methacrylic acid (MAA), were used in the graft copolymerization process. Metoprolol tartarate was then incorporated into this graft copolymer matrix, and the resultant drug delivery system was subjected to comprehensive characterization using techniques such as Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The swelling behavior of the drug delivery system was evaluated under different pH conditions, and in vitro drug release studies were conducted. Furthermore, pharmacokinetic parameters including the area under the curve (AUC), maximum plasma concentration (Cmax), time to reach Cmax (Tmax), and half-life (t1/2) were determined for metoprolol-loaded hydrogel formulations in rabbit plasma, and these results were compared with those obtained from a commercially available product. The key findings from the study include observations that higher concentrations of acrylic acid (AA) and Cydonia oblonga mucilage (CM) in the graft copolymer enhanced swelling, while the opposite trend was noted at elevated concentrations of methacrylic acid (MAA) and N, N-methylene bisacrylamide (MBA). FTIR analysis confirmed the formation of the graft copolymer and established the compatibility between the drug and the polymer. SEM imaging revealed a porous structure in the prepared formulations. Additionally, the swelling behavior and drug release profiles indicated a pH-sensitive pattern. The pharmacokinetic assessment revealed sustained release patterns of metoprolol from the hydrogel network system. Notably, the drug-loaded formulation exhibited a higher Cmax (156.48 ng/mL) compared to the marketed metoprolol product (96 ng/mL), and the AUC of the hydrogel-loaded metoprolol was 2.3 times greater than that of the marketed formulation. In conclusion, this study underscores the potential of quince seed mucilage as an intelligent material for graft-copolymer-based oral-controlled release drug delivery systems.

PH-sensitive carboxymethyl starch-gelatin coated COF/5-Fu for colon cancer therapy

Owing to the desired structure, recently covalent organic frameworks (COFs) have emerged as one of the more efficient drug-loading platforms. Therefore, in the current study, we constructed COF with a spherical structure as a platform for 5-fluorouracil (5-Fu) loading. The as-synthesized COF showed a larger pore size (∼30.42 nm) than the 5-Fu dimension and a surface area of 230.58 m2/g. With these advantages, the 5-Fu loading percentage on COFs was achieved at ∼93.33 % (COF/5-Fu). However, their imine bond is relatively unstable in harsh acidic conditions. Hence, to prevent the fast drug release at pH 1.2, and considering that the key objective of the frontier work was to construct an oral site-definite controlled drug delivery system, there is an urgent and strong need to cap COF/5-Fu into carboxymethyl starch-gelatin (CMS-Gel) coat (COF/5-Fu@CMS-Gel). Drug release tests showed that the loaded 5-Fu was released highly at pH 7.4, but only 14.11 % of 5-Fu releases occurred at pH 1.2. The structural analyses supported the hypothesis of the successful formation of the prepared samples. The MTT assay showed the biocompatible nature of neat COF@CMS-Gel and its cytotoxic potential after drug loading. All these good properties can guarantee that the COF/5-Fu@CMS-Gel is promising for controlled colon drug delivery.

Formulation and Evaluation of Hydrogel Based Oral Controlled Drug Delivery System for Saquinavir

The main aim of this study was to develop hydrogel based controlled drug delivery system of Saquinavir mesylate as hard gelatin capsule which are able to deliver the drug at prolonged rate. The hydrogel was prepared by crosslinking HPMC 15 cps and Carbopol 971P and then granules are developed using MCC as diluent. Drug excipient compatibility was studied by FT-IR. The prepared hydrogels formulation are evaluated for Swelling index. Drug release from hydrogel was performed by using Franz diffusion cell. The prepared granules are evaluated for pre formulation studies (Bulk density, Tapped density, Angle of repose). The Saquinavir hydrogel capsule are evaluated for weight variation, Drug content uniformity (95%), Disintegration time (11 mins). In-vitro drug release studies are conducted for 12hrs by using USP type I apparatus which is showing drug release of 98%. From the drug release kinetics, it can be determined that the saquinavir hydrogel capsules drug release mechanism follows both the zero-order and Higuchi models. For all metrics, the formulation SHCF4 has demonstrated the best performance in accordance with pharmacopoeia standards.

Preparation and Evaluation of Sustained Release Hydrogel Alginate Beads of Meclizine Hydrochloride

Oral controlled drug delivery systems represent the foremost widespread kind of sustained drug delivery systems for the plain blessings of oral route of drug administration. Suchsystemsrelease the drug with constant or variable unleash rates. The oral controlled releasesystems show a typical pattern of drug unleash within which the drug concentration is maintained inthe therapeutic window for a chronic amount of your time (sustained release), thereby guaranteeingsustained therapeutic action. They are used as single dosage form. Present work involvespreparation and analysis of sustained release beads of beads of Meclizine Hydrochloride using Sodium alginate as natural polymer as well as Hydroxyl Propyl Methyl Cellulose K15, Sodium CMC. The technique employed for preparation of beads of the drug is ionotropic gelation.

An Overview of Pharmaceutical Mini Tablet

The objective of controlled drug delivery systems is to decrease the frequency of dosing and to increase the efficiency of the drug by localization. In oral controlled drug delivery systems, Mini-tablets represent the new trend in Solid oral dosage forms are most acceptable dosage forms especially tablets are most widely accepted by people of different age groups. Mini tablets with a diameter alike to or smaller than 3–6 mm. mini tablets are multiple unit dosage forms and are convenient to pellets or any other oral dosage forms as there calm to manufacture and stability snags are less. Some types of mini tablets are like to Oral disintegrating mini tablets, pH responsive mini tablets, Biphasic mini tablets, gastro retentive mini tablets, paediatric mini tablets, and bio adhesive mini tablets.

Development and Characterization of Cephradine Proniosomes for Oral Controlled Drug Delivery

Abstract: The role of Proniosomes in oral controlled drug delivery system is well accepted. Presently, an attempt was made to develop cephradine (CP) Proniosomes to prolong its duration of action with better efficacy. Overall, eighteen formulation trials were developed using variable quantities of sorbitol (F0S-F8S) and maltodextrin (F0M-F8M) carriers along with span60 and cholesterol. Trials were evaluated for powder flowability, drug entrapment efficiency and in vitro drug release. Based on the mentioned characteristics, formulations F4M and F4S were optimized. Stability test was performed on optimized Proniosomes for three months at temperature (2-8°C). Comparison for antimicrobial sensitivity against Staphylococcus aureus was also made between optimized and marketed conventional CP capsule. More than 80% drug release was observed in 22 hr in the trial formulations. The optimized CP Proniosomes were found to be highly stable with % drug entrapment efficiency of 78.60±0.15 and 88.41±0.19 respectively for F4M and F4S. The prepared Proniosomes possessed higher bactericidal activity against S. aureus than reference products (M1 and M2). In conclusion, CP Proniosomes have been successfully prepared using sorbitol/maltodextrin carrier. Sorbitol carrier exhibited marginally better drug entrapment efficiency and bactericidal activity than the maltodextrin trial and marketed brands. This effort offers improved drug delivery with the potential of more effective controlled therapy. Key words: Proniosomes, Cephradine, Nano-carriers, Niosomes, Bactericidal activity, Controlled drug delivery.

Recent Trends in Floating Drug Delivery System

Conventional immediate release dosage forms does not control the drug release which leads to low oral bioavailability and more toxic effects. This happens due to multiple dosing and fluctuations in the plasma drug concentrations. Retention of the dosage forms in a specific region of the GIT provides more benefits, for those drugs which have poor absorption in stomach, low solubility and degradation in alkaline pH. FDDS is one among the important system with gastric retention properties. Formulations designed as FDDS, controls the rate of drug release by prolonging the gastric retention for extended hours and improves the absorption as well as bioavailability. This article provides information on recent trends of research and development in FDDS with a special emphasis on its importance for oral controlled drug delivery system. This review article also provides information on category of drugs and different polymers used for FDDS.

In vivo Evaluation of Theophylline Sustained Release Matrix Tablets Containing Low Viscosity Guar Gum

The present investigation was carried out to evaluate the utility of guar gum as a hydrophilic matrix carrier in the design of oral controlled drug delivery. Based on the earlier reports, the low viscosity guar gum appears to be superior to medium and high viscosity grades of guar gum in providing a sustained delivery of theophylline along the GI tract. Conducting in vivo studies on theophylline matrix tablets containing 10% of low viscosity guar gum as a representative formulation assessed the in vivo performance of the guar gum matrix tablets. The in vivo studies were carried out in dogs. The effective concentration of theophylline was sustained for a period of 16 hours. The extended tmax, reduced absorption rate constant, prolonged MRT, unchanged Cmax and unchanged bioavailability indicate a controlled release of theophylline from the guar gum matrix tablets resulting in a sustained absorption and prolonged blood levels of theophylline. The theophylline matrix tablets showed blood levels well below 15 ?g/mL indicating freedom from adverse effects. Based on the studies, guar gum appears to be a potential carrier in the design of oral controlled drug delivery systems.

Raft Forming Systems: A Novel Approach to Gastric Retention


 Oral delivery of drug is the most preferable drug delivery due to the ease of administration, patient compliance and flexibility in the formulations. In recent era various technologies have been made in research and development of oral controlled release drug delivery system to overcome various physiological difficulties such as variation in gastric retention and emptying time. Conventional oral dosage forms pose low bioavailability problems due to their rapid gastric transition from stomach, especially in case of drugs which are less soluble at alkaline pH of intestine and locally acting drugs in stomach get rapidly emptied. So, frequency of dose administration in such cases is increased. Gastro retentive drug delivery system (GRDDS) is facing many challenges which can be overcome by upcoming newly emerging approach, raft forming systems (RFS). The present study provides valuable information and highlights advances in this raft forming system. Different types of smart polymers used for their formulation have also been summarized. The current review focuses on the mechanism, formulation development and evaluation aspects of the raft forming systems and also highlights parameters which may lead to response variations in altered physiological conditions are discussed as well.

Formulation and Evaluation of Sustained Release Matrix Tablets of Aceclofenac

This study aimed to improve the dissolution rate of aceclofenac and release the drug in a controlled manner over a period of 24 hours. Matrix tablets were prepared by direct compression method, using hydrophilic polymers (HPMC/guar gum). Matrix tablets were prepared by wet granulation method using different hydrophilic polymers (HPMC/guar gum). Tablets were evaluated for in vitro drug release profile in phosphate buffer with pH 6.8 (without enzymes). The thickness and hardness of prepared tablets were 3.23 ± 0.035 to 3.28 ± 0.008 mm and 3.26 ± 0.115 to 3.60 ± 0.200 kg/cm2, respectively. The friability was within the acceptable limits of pharmacopoeial specifications (0.31 to 0.71%), which indicates the good mechanical strength of the tablets. Drug release was retarded with an increase in polymer concentration due to the gelling property of polymers. The in vitro drug release from the proposed system was best explained by Higuchi’s model, indicating that drug release from tablets displayed a diffusion-controlled mechanism. The results clearly indicate that guar gum could be a potential hydrophilic carrier in developing oral controlled drug delivery systems. Based on the study results, formulations F8 was selected as the best formulation.

Interpolymer Complexes Based on Eudragit<sup>®</sup> EPO/Eudragit<sup>®</sup> S100 as Carriers for Oral Controlled Drug Delivery Systems

Introduction. The possibility of obtaining IPC based on polyanions of various structures Eudragit ® , Carbopol ® , pectin, carrageenan and sodium alginate with oppositely charged polycations - Eudragit ® EPO, Eudragit ® RS/RL and chitosan, stabilized as already well-known by ionic bonds. It has been proven that interpolymer complexes with the participation of Eudragit ® copolymers could be also formatted by hydrogen bonds too as well. Prepared polycomplexes are promising carriers for drug delivery systems (DDS) to various parts of the gastrointestinal tract (GIT): the mouth (orodispersible and buccal DDS), stomach (gastroretentive DDS) and intestine (colon-specific DDS). Aim. Study of interpolymer complexes based on a pair of Eudragit ® EPO and Eudragit ® S100 copolymers obtained in a medium of various organic solvents (ethyl alcohol and a mixture of isopropanol-acetone (in a ratio of 60:40, v/v) from the point of view of their use in oral matrix systems for the delivery of active pharmaceutical ingredients. Materials and methods. The synthesis of interpolymer complexes based on Eudragit ® copolymers was carried out in organic solvents [ethyl alcohol or isopropanol-acetone mixture (in a ratio of 60:40, v/v)]. The structural features of the obtained IPCs were assessed by FTIR spectroscopy using a Nicolet iS5 instrument with a Smart iTR single ATR attachment (Thermo Scientific, USA) and differential scanning calorimetry with modulated temperature (mDSC) using a Discovery™ DSC instrument (TA Instruments, USA). The composition was determined using the method of elemental analysis on a Thermo Flash 2000 CHNS/O device (Thermo Fisher Scientific, UK). The swelling capacity of the obtained IPCs was evaluated in buffer media with pH values that mimic the pH of different parts of the gastrointestinal tract (GIT): 1.2; 5.8; 6.8 and 7.4. The release of theophylline (TEO) and diclofenac sodium (DS) was assessed on a ERWEKA DFZ II (ERWEKA GmbH, Germany) flow through cell apparatus in buffer media simulating the pH of various parts of the gastrointestinal tract for 7 hours. Results and discussion . All obtained IPCs are characterized by an excess of Eudragit ® S100 in their composition. The obtained IPCs are stabilized by a cooperative system of ionic and hydrogen bonds. DSC thermograms of IPC samples are characterized by the presence of a single glass transition temperature, which confirms the absence of impurities of free copolymers in their composition, while with an increase in the content of Eudragit ® S100 in the IPC composition, the glass transition temperature increases. The matrix based on IPC-1 disintegrated during the first 15 minutes of the experiment in a medium with pH 1.2, while matrices based on the rest of the IPC samples retain their shape for 7 hours and are characterized by pH-independent behavior. The release of TEO from polycomplex matrices is diffusion-controlled and occurs in accordance with Fick's law (IPC-2, IPC-4, and IPC-6) or can be characterized as «abnormal transport» (IPC-1, IPC-3 and IPC- 5), and also depends on the swelling capacity of the matrix. In contrast, the release of DS is dependent on surface erosion of the matrix, which is consistent with the Super Case II transport mechanism. Conclusion. The resulting interpolymer complexes Eudragit ® EPO/Eudragit ® S100 are promising carriers in matrix oral systems for the controlled delivery of active pharmaceutical ingredients, providing a prolonged release of BCS class I substances, depending on the diffusion rate from the swollen matrix, and a delayed release of BCS class II substances, controlled by surface processes erosion of the matrix.

Formulation and Development of Extended Release Matrix Tablet of Carvedilol Phosphate

Carvedilol Phosphate, a non selective β-blocker drug under BCS class П and used in treatment of Hypertension. Solubility of the drug and its bioavailability is low. The purpose of the present study is to design extended release matrix tablet of Carvedilol Phosphate to improve gastric retention and reduce gastric emptying time. All blended formulations were evaluated for bulk density, tapped density, Carr’s index, angle of repose and the Hausner’s ratio. All these results indicated that, the powder blend showed good flow properties. All tablet formulations were evaluated for weight variation, hardness, Friability, Thickness, Content uniformity, In-vitro drug release. Regulated drug release in zero-order manner attained in the current study indicates that the optimized extended release tablet of Carvedilol Phosphate, prepared using Sodium carboxymethyl cellulose and HPMC K4M can successfully be employed in oral controlled release drug delivery system. Modified release ability of the formulation is likely to increase its GI residence time, and eventually, improve the extent of bioavailability.

Clay-Polymer Nanocomposites Prepared by Reactive Melt Extrusion for Sustained Drug Release.

Clay–polymer nanocomposites have exhibited a great potential as carriers for controlled release drug delivery. This study aims to prepare exfoliated montmorillonite–Eudragit RS nanocomposites using reactive melt extrusion and investigate the influence of claying loading, clay types (sodium montmorillonite (Cloisite Na) vs. organomodified montmorillonite (Cloisite 20)) on clay–polymer interactions and drug release properties. The clays were used as the filler material at various levels in Eudragit RS and theophylline was used as the active pharmaceutical ingredient. The resulting structure of the nanocomposites was characterized using TEM (transmission electron microscopy) and XRPD (X-ray powder diffraction). The hygroscopicity of the nanocomposites was investigated using DVS (dynamic vapor sorption). The effect of the interfacial interaction between the polymer and clay sheet, the clay loading as well as the clay type on the drug release behavior were further studied by dissolution testing. TEM and XRPD data show that when the clay content is increased from 5% to 15% by weight, the nanocomposite’s structure switches from a fully exfoliated state to intercalated structures or partial exfoliation with stacked clay layers. FT-IR (fourier transform infrared spectroscopy) and ssNMR (solid-state NMR) results suggest that Cloisite Na and Cloisite 20 layers exhibit different interaction strengths with polymer networks by creating compacted complex structures. The addition of nanoclay in the formulation could robustly adjust drug release profiles, and the clay concentration and type are important factors that affect the crossing-linking density of the nanocomposites by adjusting the drug release properties. This study indicates that the clay–Eudragit RS nanocomposites provide an improved oral controlled drug delivery system that minimizes the drug dosing frequency, potentially leading to improved patient compliance.

Hot melt extruded polysaccharide blends for controlled drug delivery

Different types of hot melt extrudates were prepared based on a variety of blends of ethylcellulose with a 2nd polysaccharide, namely hydroxypropyl methylcellulose (HPMC), pectin, maize starch, inulin, maltodextrin, guar gum, and chitosan. In selected cases, the polymer:polymer blend ratio was varied from 80:20, 70:30, 60:40, 50:50, 40:60, 30:70 to 20:80. The addition of appropriate amounts of plasticizers allowed reducing the extrusion temperature to about 100 °C. The impacts of the screw speed, extrusion temperature, amount and type of plasticizer as well as of the amount and type of drug (10–60% theophylline or diprophylline) were studied. Drug release was measured in 0.1 M HCl for 2 h, followed by phosphate buffer pH 6.8 and (optionally) fecal samples to simulate the colon (under anaerobic conditions). DSC measurements and optical microscopy were used to characterize the physical state and morphology of the systems. Interestingly, hot melt extrudates based on ethylcellulose:guar gum blends could be easily prepared at a temperature of 100 °C and offered large spectra of drug release patterns for both: slightly water-soluble theophylline as well as freely water-soluble diprophylline. About constant drug release rates could be obtained during prolonged periods of time. Importantly, the resulting drug release rates from hot melt extrudates based on ethylcellulose:guar gum 80:20 blends were similar in the presence and absence of colonic bacteria, indicating that the ethylcellulose seems to protect the guar gum from degradation upon exposure to fecal samples. Furthermore, these systems were long term stable for at least 1 year under ambient conditions. Thus, they can offer an interesting potential as oral controlled drug delivery systems.

Preparation and Evaluation of Sustained Release Beads of Zolmitriptan Hydrochloride

Oral controlled drug delivery systems represent the foremost widespread kind of sustained drug delivery systems for the plain blessings of oral route of drug administration. Such systems release the drug with constant or variable unleash rates. The oral controlled release systems show a typical pattern of drug unleash within which the drug concentration is maintained in the therapeutic window for a chronic amount of your time (sustained release), there by guaranteeing sustained therapeutic action. They are used as single dosage form. Present work involves preparation and analysis of sustained release beads of beads of Zolmitriptan Hydrochloride using Sodium alginate as natural polymer as well as Hydroxyl Propyl Methyl Cellulose K15, Chitosan Hydrochloride. The technique employed for preparation of beads of the drug is ionotropic gelation.

Azadirachita indica gum based sildenafil citrate mucoadhesive microspheres – Design and optimization

The current research involved design and optimization of Sildenafil citrate loaded oral mucoadhesive multiparticulate system, to prolong residence time and enhance bioavailability of the drug. The microspheres were prepared by ionotropic gelation method using ‘Azadirachta Indica’ as a mucoadhesive polymer employing 32 factorial design. Microspheres were discrete, spherical, free flowing and the absence of drug-excipient interactions was confirmed by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. The drug release followed Fickian diffusion mechanism with zero order release kinetics. Optimization of the responses was carried out using numerical desirability and graphical approaches. In vivo pharmacokinetic studies in rabbits demonstrated an increase in mean residence time by 75% and relative bio-availability by 1.5 times. Ex vivo wash off test and radiographic studies in rabbits confirmed the adherence of the microspheres to the GI mucous layer which were retained for an extended period of time. The developed formulation can be a viable alternative to the conventional dosage forms of thrice a day dosing in pulmonary arterial hypertension. The research signified the potential of ‘Azadirachta Indica’ as a mucoadhesive polymer in the design of oral controlled drug delivery systems.