{"id":62669,"date":"2024-12-30T11:30:23","date_gmt":"2024-12-30T11:30:23","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=62669"},"modified":"2025-01-06T18:19:16","modified_gmt":"2025-01-06T18:19:16","slug":"design-and-development-of-saxagliptin-microparticles-for-diabetes","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no4\/design-and-development-of-saxagliptin-microparticles-for-diabetes\/","title":{"rendered":"Design and Development of Saxagliptin Microparticles for Diabetes"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Type 2\ndiabetes is a chronic condition that affects the way the body processes blood\nglucose1<\/sup>. It is characterized by insulin resistance, where the\nbody’s cells do not respond effectively to insulin, combined with a gradual\ndecline in insulin production from the pancreas. This leads to elevated blood\nglucose levels, which can result in various health complications over time,\nsuch as heart disease, kidney damage, and neuropathy. Risk factors for\ndeveloping type 2 diabetes include obesity, sedentary lifestyle, family\nhistory, and advanced age2<\/sup>. Management typically involves lifestyle\nchanges, such as diet and exercise, along with medications when necessary to\nhelp regulate blood sugar levels and maintain overall health3<\/sup>.<\/p>\n\n\n\n

The\nincreasing prevalence of type 2 diabetes, associated with modern lifestyles,\nhas prompted intensified research into effective management strategies4<\/sup>.\nMillions of individuals grapple with this non-insulin-dependent form of\ndiabetes, which necessitates long-term treatment often characterized by high\nrates of non-adherence. To address this challenge, sustained release drug\ndelivery systems hold significant promise for improving healthcare quality. In\nthe context of type 2 diabetes, maintaining consistent drug levels in the\nbloodstream is crucial. While novel drug development for type 2 diabetes is\nongoing, equal emphasis is being placed on creating appropriate delivery\nsystems that prolong drug action and enhance patient compliance by reducing\ndosing frequency5<\/sup>.<\/p>\n\n\n\n

Saxagliptin\nis a second-generation sulfonylurea, oral antihyperglycemic medication used to\nmanage type 2 diabetes mellitus6<\/sup>. It belongs to the class of drugs\nknown as DPP-4 inhibitors, which work by enhancing the body\u2019s incretin levels,\nleading to increased insulin secretion and decreased glucagon release in\nresponse to meals7<\/sup>. This dual action helps lower blood sugar levels\nwhile minimizing the risk of hypoglycemia8<\/sup>. Saxagliptin is often\nprescribed alongside diet and exercise and can be used alone or in combination\nwith other diabetes medications to achieve better glycemic control9,10<\/sup>.<\/p>\n\n\n\n

Microparticles\nare small particles typically ranging from 1 to 1000 micrometers in diameter,\nwidely used in various fields such as pharmaceuticals, biotechnology, and\nenvironmental science11<\/sup>. These versatile materials can be composed\nof natural or synthetic polymers, ceramics, or metals, and serve multiple\npurposes, including drug delivery, targeting, and controlled release of\ntherapeutics12<\/sup>. In drug delivery systems, microparticles can\nencapsulate active ingredients, protecting them from degradation and\nfacilitating their transport to specific sites within the body13<\/sup>.\nTheir unique size and surface characteristics also allow for functionalization,\nenabling enhanced interaction with biological systems and improved efficacy in\nmedical applications14<\/sup>.<\/p>\n\n\n\n

This\nstudy aims to develop a microparticle-based drug delivery system for Saxagliptin,\nits short biological half-life of approximately 3.1 hours necessitates frequent\ndosing (twice daily), which can contribute to non-adherence. Currently\navailable in conventional tablet forms (2.5-5 mg\/day), controlled release\nformulations present a promising solution.<\/p>\n\n\n\n

While a few formulation techniques and analytical methods for Saxagliptin have been reported15-21<\/sup>, no previous studies have focused on Saxagliptin microparticles for diabetes treatment. Therefore, this investigation seeks to design and develop novel microparticles of Saxagliptin aimed at treating diabetes22<\/sup>. This approach focuses on creating a controlled release formulation using a lower drug dose, thereby aiming to achieve consistent plasma drug concentrations. This may lead to enhanced patient compliance due to reduced dosing frequency, improved therapeutic efficacy, and minimized side effects resulting from a more controlled drug release profile.<\/p>\n\n\n\n

Materials and Methods<\/strong><\/p>\n\n\n\n

Chemicals<\/strong><\/p>\n\n\n\n

Saxagliptin was obtained as a gift sample from Shree Icon Laboratories, Vijayawada, India. Eudragit L-100 and Eudragit S-100 were commercially sourced from Loba Chemicals, Mumbai, India. All other chemicals used were of analytical grade. <\/p>\n\n\n\n

Preparation of Microparticles<\/strong><\/p>\n\n\n\n

This\nstudy employed the emulsion solvent evaporation technique for the preparation of\nmicroparticle formulations23<\/sup>. The specific compositions of each\nformulation are given in Table 1.<\/p>\n\n\n\n

Table 1: Composition of Saxagliptin microparticles<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\n

Formulation code<\/strong><\/p>\n<\/td>\n

\n

F1<\/sub><\/strong><\/p>\n<\/td>\n

\n

F2<\/sub><\/strong><\/p>\n<\/td>\n

\n

F3<\/sub><\/strong><\/p>\n<\/td>\n

\n

F4<\/sub><\/strong><\/p>\n<\/td>\n

\n

F5<\/sub><\/strong><\/p>\n<\/td>\n

\n

F6<\/sub><\/strong><\/p>\n<\/td>\n

\n

F7<\/sub><\/strong><\/p>\n<\/td>\n

\n

F8<\/sub><\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Core: Coat ratio<\/p>\n<\/td>\n

\n

1:1<\/p>\n<\/td>\n

\n

1:2<\/p>\n<\/td>\n

\n

1:3<\/p>\n<\/td>\n

\n

1:4<\/p>\n<\/td>\n

\n

1:1<\/p>\n<\/td>\n

\n

1:2<\/p>\n<\/td>\n

\n

1:3<\/p>\n<\/td>\n

\n

1:4<\/p>\n<\/td>\n<\/tr>\n

\n

Saxagliptin (mg)<\/p>\n<\/td>\n

\n

1000<\/p>\n<\/td>\n

\n

1000<\/p>\n<\/td>\n

\n

1000<\/p>\n<\/td>\n

\n

1000<\/p>\n<\/td>\n

\n

1000<\/p>\n<\/td>\n

\n

1000<\/p>\n<\/td>\n

\n

1000<\/p>\n<\/td>\n

\n

1000<\/p>\n<\/td>\n<\/tr>\n

\n

Eudragit S-100 (mg)<\/p>\n<\/td>\n

\n

1000<\/p>\n<\/td>\n

\n

2000<\/p>\n<\/td>\n

\n

3000<\/p>\n<\/td>\n

\n

4000<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n<\/tr>\n

\n

Eudragit L-100 (mg)<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

–<\/p>\n<\/td>\n

\n

1000<\/p>\n<\/td>\n

\n

2000<\/p>\n<\/td>\n

\n

3000<\/p>\n<\/td>\n

\n

4000<\/p>\n<\/td>\n<\/tr>\n

\n

Span 80 (ml)<\/p>\n<\/td>\n

\n

Q.S<\/p>\n<\/td>\n

\n

Q.S<\/p>\n<\/td>\n

\n

Q.S<\/p>\n<\/td>\n

\n

Q.S<\/p>\n<\/td>\n

\n

Q.S<\/p>\n<\/td>\n

\n

Q.S<\/p>\n<\/td>\n

\n

Q.S<\/p>\n<\/td>\n

\n

Q.S<\/p>\n<\/td>\n<\/tr>\n

\n

Acetone (ml)<\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n

\n

10<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Organic Phase\nPreparation<\/strong><\/p>\n\n\n\n

A\nmeasured amount of Saxagliptin and Eudragit (at a 1:1 ratio) was dissolved in\n10 mL of acetone to create a homogeneous drug-polymer solution.<\/p>\n\n\n\n

Emulsion Formation<\/strong><\/p>\n\n\n\n

The\norganic solution was gradually added, in a thin stream, to 100 mL of liquid\nparaffin containing 1% Span 80 surfactant. This mixture was continuously\nstirred for 1 hour to form an emulsion.<\/p>\n\n\n\n

Microparticle\nCollection<\/strong><\/p>\n\n\n\n

The\nresulting microparticles were separated from the emulsion through filtration\nand subsequently washed with petroleum ether to remove any residual organic\nsolvents24<\/sup>.<\/p>\n\n\n\n

Drying and Storage<\/strong><\/p>\n\n\n\n

Finally,\nthe microparticles were air-dried for 12 hours and stored in a desiccator for\nfurther analysis.<\/p>\n\n\n\n

Preparation of Other\nRatios<\/strong><\/p>\n\n\n\n

For\nmicroparticles with drug-to-polymer ratios of 1:2, 1:3, and 1:4, the\ncorresponding amounts of Eudragit L-100 or Eudragit S-100 were used, while\nmaintaining the overall process steps outlined above. The list of prepared\nmicroparticles was tabulated in Table 2. \n<\/p>\n\n\n\n

Table 2: List of Saxagliptin microparticles prepared<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\n

Polymers used<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Eudragit S-100<\/strong><\/p>\n<\/td>\n

\n

Eudragit L-100<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Formulation code<\/strong><\/p>\n<\/td>\n

\n

Core: Coat<\/strong><\/p>\n<\/td>\n

\n

Formulation code<\/strong><\/p>\n<\/td>\n

\n

Core: Coat<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

F-1<\/p>\n<\/td>\n

\n

1:1<\/p>\n<\/td>\n

\n

F-5<\/p>\n<\/td>\n

\n

1:1<\/p>\n<\/td>\n<\/tr>\n

\n

F-2<\/p>\n<\/td>\n

\n

1:2<\/p>\n<\/td>\n

\n

F-6<\/p>\n<\/td>\n

\n

1:2<\/p>\n<\/td>\n<\/tr>\n

\n

F-3<\/p>\n<\/td>\n

\n

1:3<\/p>\n<\/td>\n

\n

F-7<\/p>\n<\/td>\n

\n

1:3<\/p>\n<\/td>\n<\/tr>\n

\n

F-4<\/p>\n<\/td>\n

\n

1:4<\/p>\n<\/td>\n

\n

F-8<\/p>\n<\/td>\n

\n

1:4<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

Characterization of\nMicroparticles<\/strong><\/p>\n\n\n\n

The\nmicroparticles were assessed for their flow properties using standard methods,\nproviding insights into their handling characteristics during production and\nformulation development25<\/sup>.<\/p>\n\n\n\n

Drug Entrapment\nEfficiency<\/strong><\/p>\n\n\n\n

To\nquantify the microparticles, an accurate weight of 100 mg was crushed and\ndissolved in 100 mL of pH 6.8 phosphate buffer, and absorbance was measured at\n210 nm-a standard technique for quantifying Saxagliptin.<\/p>\n\n\n\n

Drug Loading and\nEncapsulation Efficiency Calculations<\/strong><\/p>\n\n\n\n

The\npercentage of drug loading within the microparticles (L) and encapsulation\nefficiency (E) were calculated using standard formulas26<\/sup>.<\/p>\n\n\n\n

In-Vitro<\/em> Release Studies<\/strong><\/p>\n\n\n\n

The USP\nXXIII apparatus was utilized at 37\u00b0C\u00b10.5\u00b0C, with a rotation speed of 100 rpm\nthroughout the experiment. Samples (5 mL) were withdrawn and analyzed at 210\nnm.<\/p>\n\n\n\n

Release Kinetics\nAnalysis<\/strong><\/p>\n\n\n\n

The data\nwere analyzed using standard models to explore the release mechanisms. By\nfitting the dissolution data to these models, researchers aimed to identify the\ndominant mechanism governing drug release from the Saxagliptin microparticles27<\/sup>.<\/p>\n\n\n\n

Microscopic\nEvaluation with SEM<\/strong><\/p>\n\n\n\n

Scanning\nElectron Microscopy (SEM) was performed using a SEM-JEOL JSM 6360A model to\nexamine the surface morphology of both loaded and unloaded microparticles at\nvarious magnifications. This imaging technique provided valuable insights into\nvarious characteristics of the microparticles28<\/sup>.<\/p>\n\n\n\n

Compatibility\nAssessment Using IR Spectroscopy<\/strong><\/p>\n\n\n\n

FTIR\nanalysis was conducted using the KBr pellet technique to obtain the infrared\nspectra. The spectra were collected in transmittance mode at a resolution of 4\ncm\u207b\u00b9 and a wave number range of 380 to 4368 cm\u207b\u00b9. By comparing the spectra,\nresearchers assessed potential interactions between the drug and excipients\nwithin the microparticles.<\/p>\n\n\n\n

Microparticle\nCharacteristics and Process Optimization<\/strong><\/p>\n\n\n\n

The\nemulsion solvent evaporation technique successfully produced discrete,\nspherical microparticles with good flowability and minimal stickiness, both\nindividually and as aggregates. This technique relies on creating a stable\nemulsion during the initial stages to ensure isolated microparticles29<\/sup>.<\/p>\n\n\n\n

Impact of Emulsifier\nConcentration<\/strong><\/p>\n\n\n\n

A critical factor influencing microparticle size is the concentration of the emulsifier (Span 80) used. An optimal concentration is essential for achieving the finest and most stable dispersion. In below optimal concentration, insufficient reduction in interfacial tension leads to the fusion of dispersed droplets, resulting in larger globules and, consequently, larger microparticles. In above optimal concentration, although a higher emulsifier concentration may further reduce interfacial tension, it does not significantly decrease particle size. Through optimization, a Span 80 concentration of 1.5% was identified as ideal.<\/p>\n\n\n\n

Influence of\nParticle Size and Polymer Concentration<\/strong><\/p>\n\n\n\n

Microscopic\nanalysis revealed spherical microparticles, either as discrete entities or\naggregates, with particle sizes ranging from 153.23 to 189.56 \u03bcm. An increase\nin polymer concentration resulted in a larger mean particle size, attributed to\nthe increased viscosity of the internal phase with higher polymer content,\nleading to larger emulsion droplets and ultimately larger microparticles30<\/sup>.<\/p>\n\n\n\n

Impact of\nCore-to-Coat Ratio<\/strong><\/p>\n\n\n\n

This study aimed to investigate how the concentration of coating material (polymer) affects the release rate of Saxagliptin from the microparticles. <\/p>\n\n\n\n

Results and Discussion<\/strong><\/p>\n\n\n\n

The\nmicroparticles were evaluated for various properties. Particle size\ndistribution was determined by size analysis. Flowability of the microparticles\nwas assessed. Good flow properties are desirable for efficient handling and\nprocessing during manufacturing and formulation development. The percentage of\ndrug successfully encapsulated within the microparticles was quantified. High\nencapsulation efficiency indicates minimal drug loss during the preparation process,\nwith results detailed in Table 3.<\/p>\n\n\n\n

Table 3: Evaluation data of Saxagliptin microparticles<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Formulation<\/strong><\/p>\n<\/td>\n

\n

Angle of<\/strong><\/p>\n

repose<\/strong><\/p>\n<\/td>\n

\n

Bulk density<\/strong><\/p>\n

(g\/cm3<\/sup>)<\/strong><\/p>\n<\/td>\n

\n

Tapped density<\/strong><\/p>\n

(g\/cm3<\/sup>)<\/strong><\/p>\n<\/td>\n

\n

Carr\u2019s<\/strong><\/p>\n

index<\/strong><\/p>\n<\/td>\n

\n

Hausner\u2019s<\/strong><\/p>\n

ratio<\/strong><\/p>\n<\/td>\n

\n

Average particle size (\u00b5m)<\/strong><\/p>\n<\/td>\n

\n

%Drug content<\/strong><\/p>\n<\/td>\n

\n

%Encapsulation<\/strong><\/p>\n

efficiency<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

F-1<\/p>\n<\/td>\n

\n

    26.37\u00b1       0.12<\/p>\n<\/td>\n

\n

  0.350\u00b1<\/p>\n

  0.012<\/p>\n<\/td>\n

\n

   0.408\u00b1<\/p>\n

   0.011<\/p>\n<\/td>\n

\n

     14.21\u00b1<\/p>\n

    0.022<\/p>\n<\/td>\n

\n

   1.161\u00b1<\/p>\n

   0.014<\/p>\n<\/td>\n

\n

153.26<\/p>\n<\/td>\n

\n

47.27<\/p>\n<\/td>\n

\n

94.54<\/p>\n<\/td>\n<\/tr>\n

\n

F-2<\/p>\n<\/td>\n

\n

  25.65\u00b1    0.10<\/p>\n<\/td>\n

\n

  0.320\u00b1<\/p>\n

0.020<\/p>\n<\/td>\n

\n

  0.370\u00b1<\/p>\n

0.009<\/p>\n<\/td>\n

\n

     11.89\u00b1<\/p>\n

   0.009<\/p>\n<\/td>\n

\n

  1.134\u00b1<\/p>\n

0.017<\/p>\n<\/td>\n

\n

164.32<\/p>\n<\/td>\n

\n

31.56<\/p>\n<\/td>\n

\n

94.68<\/p>\n<\/td>\n<\/tr>\n

\n

F-3<\/p>\n<\/td>\n

\n

  22.76\u00b1   0.08<\/p>\n<\/td>\n

\n

  0.319\u00b1<\/p>\n

  0.005<\/p>\n<\/td>\n

\n

  0.362\u00b1<\/p>\n

  0.021<\/p>\n<\/td>\n

\n

    11.87\u00b1<\/p>\n

   0.017<\/p>\n<\/td>\n

\n

  1.130\u00b1<\/p>\n

  0.024<\/p>\n<\/td>\n

\n

178.37<\/p>\n<\/td>\n

\n

23.85<\/p>\n<\/td>\n

\n

95.40<\/p>\n<\/td>\n<\/tr>\n

\n

F-4<\/p>\n<\/td>\n

\n

   21.13\u00b1   0.11<\/p>\n<\/td>\n

\n

  0.276\u00b1<\/p>\n

  0.014<\/p>\n<\/td>\n

\n

   0.314\u00b1<\/p>\n

  0.013<\/p>\n<\/td>\n

\n

    12.10\u00b1<\/p>\n

  0.024<\/p>\n<\/td>\n

\n

  1.137\u00b1<\/p>\n

0.012<\/p>\n<\/td>\n

\n

189.56<\/p>\n<\/td>\n

\n

19.13<\/p>\n<\/td>\n

\n

95.65<\/p>\n<\/td>\n<\/tr>\n

\n

F-5<\/p>\n<\/td>\n

\n

  28.35\u00b1 0.09<\/p>\n<\/td>\n

\n

  0.271\u00b1<\/p>\n

0.021<\/p>\n<\/td>\n

\n

  0.316\u00b1<\/p>\n

  0.011<\/p>\n<\/td>\n

\n

   14.24\u00b1<\/p>\n

   0.019<\/p>\n<\/td>\n

\n

1.166\u00b1<\/p>\n

0.019<\/p>\n<\/td>\n

\n

153.23<\/p>\n<\/td>\n

\n

47.78<\/p>\n<\/td>\n

\n

95.56<\/p>\n<\/td>\n<\/tr>\n

\n

F-6<\/p>\n<\/td>\n

\n

   26.39\u00b1 0.08<\/p>\n<\/td>\n

\n

  0.314\u00b1<\/p>\n

0.018<\/p>\n<\/td>\n

\n

   0.366\u00b1<\/p>\n

  0.019<\/p>\n<\/td>\n

\n

   14.20\u00b1<\/p>\n

   0.027<\/p>\n<\/td>\n

\n

1.165\u00b1<\/p>\n

0.011<\/p>\n<\/td>\n

\n

168.56<\/p>\n<\/td>\n

\n

31.93<\/p>\n<\/td>\n

\n

95.79<\/p>\n<\/td>\n<\/tr>\n

\n

F-7<\/p>\n<\/td>\n

\n

 24.17\u00b1 0.06<\/p>\n<\/td>\n

\n

0.255\u00b10.025<\/p>\n<\/td>\n

\n

0.291\u00b1<\/p>\n

  0.005<\/p>\n<\/td>\n

\n

12.37\u00b1<\/p>\n

0.024<\/p>\n<\/td>\n

\n

 1.142\u00b1<\/p>\n

  0.014<\/p>\n<\/td>\n

\n

    177.45<\/p>\n<\/td>\n

\n

24.08<\/p>\n<\/td>\n

\n

96.32<\/p>\n<\/td>\n<\/tr>\n

\n

F-8<\/p>\n<\/td>\n

\n

 22.86\u00b1 0.04<\/p>\n<\/td>\n

\n

0.353\u00b10.027<\/p>\n<\/td>\n

\n

0.400\u00b1<\/p>\n

0.014<\/p>\n<\/td>\n

\n

11.75\u00b1<\/p>\n

0.017<\/p>\n<\/td>\n

\n

  1.133\u00b1<\/p>\n

    0.027<\/p>\n<\/td>\n

\n

    188.64<\/p>\n<\/td>\n

\n

19.17<\/p>\n<\/td>\n

\n

95.85<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

The\nmicroparticles underwent in-vitro<\/em> dissolution testing to simulate drug\nrelease within the body. The release profiles of Saxagliptin microparticles\nprepared with Eudragit S-100 and Eudragit L-100 are illustrated in Figure 1 and\n2.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 1: Release profiles of Saxagliptin microparticles prepared with Eudragit S-100<\/strong><\/p>\n<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Figure 2: Release profiles of Saxagliptin microparticles prepared with Eudragit L-100<\/strong><\/p>\n<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

To\nunderstand the underlying mechanisms governing drug release from the\nmicroparticles, peppas plots were constructed. These plots were linear for all\nmicroparticle formulations, with details of the release kinetics summarized in\nTable 4.<\/p>\n\n\n\n

Table 4: In-vitro<\/em> dissolution kinetics parameters of Saxagliptin microparticles<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Formulation code<\/strong><\/p>\n<\/td>\n

\n

Correlation coefficient (r2<\/sup>)<\/strong><\/p>\n<\/td>\n

\n

Release kinetics<\/strong><\/p>\n<\/td>\n

\n

Diffusion<\/strong><\/p>\n

exponent value (n)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Zero order<\/strong><\/p>\n<\/td>\n

\n

First order<\/strong><\/p>\n<\/td>\n

\n

Higuchi<\/strong><\/p>\n<\/td>\n

\n

Peppas<\/strong><\/p>\n<\/td>\n

\n

K o<\/sub><\/strong><\/p>\n

(mg\/hr)<\/strong><\/p>\n<\/td>\n

\n

T50<\/sub><\/strong><\/p>\n

(hr)<\/strong><\/p>\n<\/td>\n

\n

T90<\/sub><\/strong><\/p>\n

(hr)<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

F1<\/p>\n<\/td>\n

\n

0.9992<\/p>\n<\/td>\n

\n

0.7949<\/p>\n<\/td>\n

\n

0.9128<\/p>\n<\/td>\n

\n

0.9998<\/p>\n<\/td>\n

\n

0.55<\/p>\n<\/td>\n

\n

4.6<\/p>\n<\/td>\n

\n

8.2<\/p>\n<\/td>\n

\n

1.0591<\/p>\n<\/td>\n<\/tr>\n

\n

F2<\/p>\n<\/td>\n

\n

0.9990<\/p>\n<\/td>\n

\n

0.8165<\/p>\n<\/td>\n

\n

0.9135<\/p>\n<\/td>\n

\n

0.9993<\/p>\n<\/td>\n

\n

0.48<\/p>\n<\/td>\n

\n

5.1<\/p>\n<\/td>\n

\n

9.2<\/p>\n<\/td>\n

\n

1.1013<\/p>\n<\/td>\n<\/tr>\n

\n

F3<\/p>\n<\/td>\n

\n

0.9974<\/p>\n<\/td>\n

\n

0.7757<\/p>\n<\/td>\n

\n

0.9031<\/p>\n<\/td>\n

\n

0.9994<\/p>\n<\/td>\n

\n

0.44<\/p>\n<\/td>\n

\n

5.9<\/p>\n<\/td>\n

\n

10.6<\/p>\n<\/td>\n

\n

1.0791<\/p>\n<\/td>\n<\/tr>\n

\n

F4<\/p>\n<\/td>\n

\n

0.9980<\/p>\n<\/td>\n

\n

0.6792<\/p>\n<\/td>\n

\n

0.9034<\/p>\n<\/td>\n

\n

0.9988<\/p>\n<\/td>\n

\n

0.41<\/p>\n<\/td>\n

\n

6.2<\/p>\n<\/td>\n

\n

11.1<\/p>\n<\/td>\n

\n

1.1032<\/p>\n<\/td>\n<\/tr>\n

\n

F5<\/p>\n<\/td>\n

\n

0.9997<\/p>\n<\/td>\n

\n

0.8049<\/p>\n<\/td>\n

\n

0.9292<\/p>\n<\/td>\n

\n

0.9992<\/p>\n<\/td>\n

\n

0.58<\/p>\n<\/td>\n

\n

4.3<\/p>\n<\/td>\n

\n

7.7<\/p>\n<\/td>\n

\n

0.9213<\/p>\n<\/td>\n<\/tr>\n

\n

F6<\/p>\n<\/td>\n

\n

0.9994<\/p>\n<\/td>\n

\n

0.8241<\/p>\n<\/td>\n

\n

0.9260<\/p>\n<\/td>\n

\n

0.9973<\/p>\n<\/td>\n

\n

0.51<\/p>\n<\/td>\n

\n

4.8<\/p>\n<\/td>\n

\n

8.7<\/p>\n<\/td>\n

\n

0.9403<\/p>\n<\/td>\n<\/tr>\n

\n

F7<\/p>\n<\/td>\n

\n

0.9987<\/p>\n<\/td>\n

\n

0.7905<\/p>\n<\/td>\n

\n

0.9326<\/p>\n<\/td>\n

\n

0.9983<\/p>\n<\/td>\n

\n

0.47<\/p>\n<\/td>\n

\n

5.2<\/p>\n<\/td>\n

\n

9.4<\/p>\n<\/td>\n

\n

0.9333<\/p>\n<\/td>\n<\/tr>\n

\n

F8<\/p>\n<\/td>\n

\n

0.9998<\/p>\n<\/td>\n

\n

0.7651<\/p>\n<\/td>\n

\n

0.9239<\/p>\n<\/td>\n

\n

0.999<\/p>\n<\/td>\n

\n

0.43<\/p>\n<\/td>\n

\n

5.7<\/p>\n<\/td>\n

\n

10.3<\/p>\n<\/td>\n

\n

0.9438<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

For\nmicroparticles prepared using Eudragit S-100, the exponential coefficient (n)\nvalues ranged from 1.0591 to 1.1032, indicating a super case-II transport\nmechanism. In contrast, microparticles formulated with Eudragit L-100 exhibited\nn values of 0.9213 to 0.9438, suggesting an anomalous diffusion process\ninfluenced by both diffusion and other mechanisms such as erosion or swelling\nof the polymer matrix. The results also indicated a correlation between the\nconcentrations of coating material applied and the release rate, with increased\ncoating material concentration enhancing wall thickness and consequently\nslowing drug release. This highlights the ability to control drug release by\nadjusting the polymer-to-drug ratio within the microparticles. FTIR spectroscopy\nwas employed to evaluate potential interactions between Saxagliptin and the\nexcipients used in the optimized microparticle formulation. Scanning electron\nmicroscopy (SEM) images of the drug-loaded microparticles revealed a\npredominantly spherical morphology, as illustrated in Figure 3.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 3: SEM of optimized Saxagliptin microparticles<\/strong><\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

Formulations\nprepared with Eudragit S-100 displayed a slower drug release profile compared\nto those using Eudragit L-100, highlighting the influence of polymer selection\non the release characteristics of drug formulations. Eudragit S-100 is a\npH-sensitive polymer that remains insoluble in gastric conditions but dissolves\nin the intestinal environment, making it suitable for enteric-coated systems.\nIn contrast, Eudragit L-100, which is soluble at lower pH levels, tends to\nfacilitate a quicker drug release. The differences in the release profiles can\nbe attributed to the distinct solubility characteristics of these polymers,\nwhich affect the diffusion pathways and interaction with the drug.\nConsequently, the choice of polymer not only influences the rate of drug\nrelease but also the overall efficacy and therapeutic outcome of the\nformulation.<\/p>\n\n\n\n

Particularly,\nmicroparticles prepared with a 1:2 Eudragit S-100 to drug ratio exhibited\ncontrolled drug release for up to 12 hours, indicating a sustained delivery\nsystem that can be beneficial for prolonged therapeutic effects. The\ndissolution studies conducted revealed zero-order release kinetics, suggesting\nthat the drug is released at a constant rate over time, independent of its\nconcentration. This is a desirable feature for many therapeutic agents, as it\nallows for predictable and stable drug levels in circulation. The Peppas model\nfurther elucidated the mechanism of drug release, indicating a combination of\ndiffusion and erosion processes, which govern how the drug is released from the\npolymer matrix. These findings underscore the potential of Eudragit S-100 based\nformulations in achieving controlled drug delivery systems that enhance patient\ncompliance and therapeutic effectiveness.<\/p>\n\n\n\n

Acknowledgement<\/strong><\/p>\n\n\n\n

We acknowledge V. V. Institute of Pharmaceutical Sciences, Gudlavalleru for proving necessary support for carryout the research work. <\/p>\n\n\n\n

Funding Sources<\/strong><\/p>\n\n\n\n

The author(s) received no financial support for the research, authorship, and\/or publication of this article.<\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

The author(s) do not have any conflict of interest.<\/p>\n\n\n\n

Data Availability Statement<\/strong><\/p>\n\n\n\n

This statement does not apply to this article.<\/p>\n\n\n\n

Ethics Statement<\/strong><\/p>\n\n\n\n

This research did not involve human participants, animal subjects, or any material that requires ethical approval.<\/p>\n\n\n\n

Informed Consent Statement<\/strong><\/p>\n\n\n\n

This study did not involve human participants, and therefore, informed consent was not required.<\/p>\n\n\n\n

Clinical Trial Registration<\/strong><\/p>\n\n\n\n

This\nresearch does not involve any clinical trials.<\/p>\n\n\n\n

Author Contributions<\/strong><\/p>\n\n\n\n

Lakshmana\nRao Atmakuri: Conceptualization,\nMethodology, Original Draft.<\/p>\n\n\n\n

Jhansi\nNelapati:\nData Collection, Analysis.  <\/p>\n\n\n\n

Bhaskar Vallamkonda: Visualization, Supervision. <\/p>\n\n\n\n

Ranadheer Reddy Challa: Funding Acquisition, Resources. <\/p>\n\n\n\n

Subrahmanya\nSai Malleswara Sharma Sonti: Writing, Project Administration.<\/p>\n\n\n\n

Krishna Sudarsana\nBhuvanagiri:\nReview, Editing.<\/p>\n\n\n\n

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    CrossRef <\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Introduction Type 2 diabetes is a chronic condition that affects […]<\/p>\n","protected":false},"author":15,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[119],"tags":[],"class_list":["post-62669","post","type-post","status-publish","format-standard","hentry","category-vol17no4"],"_links":{"self":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/62669","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/comments?post=62669"}],"version-history":[{"count":5,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/62669\/revisions"}],"predecessor-version":[{"id":63525,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/posts\/62669\/revisions\/63525"}],"wp:attachment":[{"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/media?parent=62669"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/categories?post=62669"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biomedpharmajournal.org\/staging\/wp-json\/wp\/v2\/tags?post=62669"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}