A Composition and Method for Preparing Solid Lipid Nanoparticles for Co-Delivery of HIV Antiretrovirals

Abstract

ABSTRACT: Title: A Composition and Method for Preparing Solid Lipid Nanoparticles for Co-Delivery of HIV Antiretrovirals The present disclosure proposes a composition for preparing solid lipid nanoparticles (SLNs) (100) for co-delivery of HIV antiretrovirals. The composition comprises 45 to 47.2 weight percentage of stearic acid (102), 9 to 9.5 weight percentage of oleic acid (104), 4 to 4.8 weight percentage of polysorbate 80 (106), 4 to 4.8 weight percentage of Span 60 (108), 9 to 9.5 weight percentage of polyvinyl alcohol (PVA) (110), 15 to 19 weight percentage of polyethylene glycol (PEG) (112), 2 to 3 weight percentage of emtricitabine (114), and 2 to 3 weight percentage of tenofovir (116). The composition provides solid lipid nanoparticles (100) with enhanced bioavailability, stability, and controlled drug release of the emtricitabine (114) and the tenofovir (116). The solid lipid nanoparticle (100) improves the solubility of antiretroviral drugs and extends their circulation time in the body.

Specification

Description:DESCRIPTION:
Field of the invention:
[0001] The present disclosure generally relates to the technical field of pharmaceutical drug delivery systems, in specific, relates to a composition and method for preparing solid lipid nanoparticles for co-delivery of HIV antiretrovirals such as emtricitabine and tenofovir, thereby enhancing therapeutic efficacy, stability, and bioavailability in the treatment of HIV infection.
Background of the invention:
[0002] HIV (Human Immunodeficiency Virus) treatment relies on antiretroviral therapy (ART), which has been instrumental in improving the health outcomes of infected individuals. Among the most commonly used drugs are emtricitabine and tenofovir, known for their efficacy in suppressing viral replication. However, the effectiveness of these drugs is often hampered by various limitations in their conventional formulations, which directly affect patient adherence and long-term treatment success.

[0003] One of the primary challenges in HIV therapy is the poor oral bioavailability of these drugs. Both emtricitabine and tenofovir face significant degradation in the gastrointestinal tract, which results in a reduced concentration of the active drug reaching systemic circulation. This limitation necessitates higher dosages to achieve therapeutic effects, increasing the potential for toxicity and adverse side effects, which are serious concerns in long-term HIV treatment. Another critical issue with current formulations is the short half-life of both drugs, which requires frequent dosing to maintain effective plasma concentrations. Patients are often required to adhere to daily or twice-daily dosing regimens, leading to issues with compliance. Poor adherence is a major concern in HIV treatment, as inconsistent dosing can lead to the development of viral resistance, reducing the effectiveness of the therapy over time.

[0004] Stability is also a key concern in existing formulations. Emtricitabine and tenofovir are sensitive to environmental conditions, such as temperature and humidity, which can compromise their stability and shelf life. These issues are particularly problematic in regions with limited access to climate-controlled storage facilities, where the distribution and long-term storage of these medications can become a logistical challenge.

[0005] Conventional drug formulations often fail to achieve adequate distribution in the body. Effective HIV treatment requires that the drugs reach viral reservoirs, such as lymph nodes and the central nervous system, where the virus can hide and persist. Existing formulations do not adequately address the need for targeting these reservoirs, which limits their ability to achieve long-term viral suppression and contributes to the persistence of HIV in the body. Another limitation of the current treatments is the systemic toxicity associated with higher doses of tenofovir, which has been linked to kidney damage and decreased bone density. The long-term use of such drugs requires a balance between efficacy and minimizing adverse effects, and conventional formulations have yet to achieve this balance. Reducing toxicity without compromising efficacy remains a significant challenge.

[0006] Furthermore, conventional drug formulations often utilize immediate-release mechanisms, which release the entire dose at once, causing rapid spikes in drug concentration. These fluctuations can lead to suboptimal therapeutic effects and increase the likelihood of drug resistance over time. The lack of controlled-release mechanisms in existing formulations is a critical gap that needs to be addressed to improve HIV treatment outcomes. Some nanoparticle-based drug delivery systems have been explored as alternatives; however, they often encounter issues related to particle size uniformity. Inconsistent particle sizes lead to variable drug release profiles, reducing the reliability of these formulations. Additionally, larger nanoparticles are prone to aggregation, which can further decrease the bioavailability and effectiveness of the treatment.

[0007] The absence of targeted delivery mechanisms in conventional formulations presents another significant limitation. Current treatments rely on passive diffusion for drug absorption, which does not guarantee that the drugs will reach critical sites of viral replication. Without targeted delivery, drugs fail to address key viral reservoirs, leaving patients at risk for incomplete viral suppression. Finally, the manufacturing processes involved in creating nanoparticle-based formulations can be complex and difficult to scale. Techniques such as high-pressure homogenization or solvent evaporation require specialized equipment and expertise, limiting their widespread adoption. This complexity poses challenges in producing cost-effective treatments, particularly in resource-limited settings where advanced infrastructure may not be available.

[0008] By addressing all the above-mentioned problems, there is a need for a composition and method for preparing solid lipid nanoparticles for co-delivery of HIV antiretrovirals such as emtricitabine and tenofovir, thereby enhancing therapeutic efficacy, stability, and bioavailability in the treatment of HIV infection. There is also a need for a solid lipid nanoparticle that encapsulates emtricitabine and tenofovir using a combination of lipids and surfactants, which ensures a controlled release of the drugs. There is also a need for a solid lipid nanoparticle that improves the solubility of antiretroviral drugs and extends their circulation time in the body. There is also a need for a solid lipid nanoparticle that reduces the systemic toxicity associated with tenofovir by using a lipid matrix for controlled drug release and reduced peak plasma concentrations.

[0009] Additionally, there is also a need for a solid lipid nanoparticle that ensures the drugs are homogeneously dispersed within the lipid matrix for effective co-delivery of both emtricitabine and tenofovir. There is also a need for a solid lipid nanoparticle that improves patient compliance by reducing the frequency of dosing through a controlled-release mechanism. There is also a need for a solid lipid nanoparticle that utilizes oleic acid to enhance the solubilization of emtricitabine and tenofovir within the lipid matrix. There is also a need for a solid lipid nanoparticle that addresses the challenges of poor drug absorption in HIV treatment, thereby ensuring efficient distribution to key viral reservoirs in the body. Further, there is also a need for a solid lipid nanoparticle that utilizes stearic acid as a solid lipid matrix for a controlled and sustained release of the active pharmaceutical ingredients (APIs).
Objectives of the invention:
[0010] The primary objective of the present invention is to provide a composition and method for preparing solid lipid nanoparticles for co-delivery of HIV antiretrovirals such as emtricitabine and tenofovir, thereby enhancing therapeutic efficacy, stability, and bioavailability in the treatment of HIV infection.

[0011] Another objective of the present invention is to provide a solid lipid nanoparticle that encapsulates emtricitabine and tenofovir using a combination of lipids and surfactants, which ensures controlled release of the drugs.

[0012] Another objective of the present invention is to provide a solid lipid nanoparticle that improves the solubility of antiretroviral drugs and extends their circulation time in the body.

[0013] Another objective of the present invention is to provide a solid lipid nanoparticle that reduces the systemic toxicity associated with tenofovir by using a lipid matrix for controlled drug release and reduced peak plasma concentrations.

[0014] Another objective of the present invention is to provide a solid lipid nanoparticle that ensures the drugs are homogeneously dispersed within the lipid matrix for effective co-delivery of both emtricitabine and tenofovir.

[0015] Another objective of the present invention is to provide a solid lipid nanoparticle that improves patient compliance by reducing the frequency of dosing through a controlled-release mechanism.

[0016] Another objective of the present invention is to provide a solid lipid nanoparticle that utilizes oleic acid to enhance the solubilization of emtricitabine and tenofovir within the lipid matrix.

[0017] Yet another objective of the present invention is to provide a solid lipid nanoparticle that addresses the challenges of poor drug absorption in HIV treatment, thereby ensuring efficient distribution to key viral reservoirs in the body.

[0018] Further objective of the present invention is to provide a solid lipid nanoparticle that utilizes stearic acid as a solid lipid matrix for a controlled and sustained release of the active pharmaceutical ingredients (APIs).
Summary of the invention:
[0019] The present disclosure proposes a composition and method for preparing solid lipid nanoparticle for co-delivery of HIV antiretrovirals. The following presents a simplified summary in order to provide a basic understanding of some aspects of the claimed subject matter. This summary is not an extensive overview. It is not intended to identify key/critical elements or to delineate the scope of the claimed subject matter. Its sole purpose is to present some concepts in a simplified form as a prelude to the more detailed description that is presented later.

[0020] In order to overcome the above deficiencies of the prior art, the present disclosure is to solve the technical problem to provide a composition and method for preparing solid lipid nanoparticles for co-delivery of HIV antiretrovirals such as emtricitabine and tenofovir, thereby enhancing therapeutic efficacy, stability, and bioavailability in the treatment of HIV infection.

[0021] According to one aspect, the invention provides a composition for preparing solid lipid nanoparticles (SLNs). In one embodiment herein, the composition comprises 45 to 47.2 weight percentage of stearic acid, 9 to 9.5 weight percentage of oleic acid, 4 to 4.8 weight percentage of polysorbate 80, 4 to 4.8 weight percentage of Span 60, 9 to 9.5 weight percentage of polyvinyl alcohol (PVA), 15 to 19 weight percentage of polyethylene glycol (PEG), 2 to 3 weight percentage of emtricitabine, and 2 to 3 weight percentage of tenofovir. The composition provides solid lipid nanoparticles with enhanced bioavailability, stability, and controlled drug release of the emtricitabine and the tenofovir.

[0022] In one embodiment herein, the stearic acid obtains a solid lipid matrix to provide controlled release of the emtricitabine and the tenofovir. In one embodiment herein, the polysorbate 80 and the Span 60 are used as surfactants to stabilize the solid lipid nanoparticles and reduce particle size. In one embodiment herein, the oleic acid is used as a lipophilic enhancer to facilitate the incorporation and solubilization of the emtricitabine and the tenofovir within the solid lipid matrix.

[0023] In one embodiment herein, the polyvinyl alcohol (PVA) is used as a stabilizer to maintain solid lipid nanoparticle stability during the formulation process and storage. In one embodiment herein, the polyethylene glycol (PEG) enhances the solubility and bioavailability of emtricitabine and the tenofovir and improves the circulation time within the body. In one embodiment herein, the solid lipid nanoparticles (SLNs) are spherical in shape and have a particle size of approximately 100 nm which enhances drug absorption, and a zeta potential of at least ±25 mV. In one embodiment herein, the solid lipid nanoparticles (SLNs) exhibit improved stability for long-term storage at a temperature of at least 4°C. The solid lipid nanoparticles (SLNs) are evaluated for size, zeta potential, and drug release profile to ensure uniformity and performance.

[0024] According to another aspect, the invention provides a method for preparing solid lipid nanoparticles for co-delivery of HIV antiretrovirals. At one step, the stearic acid is melted at a temperature of at least 60°C to obtain a lipid phase. At another step, the oleic acid is added to the melted stearic acid to obtain a homogeneous lipid mixture. At another step, the polyvinyl alcohol (PVA) and the polyethylene glycol (PEG) are dissolved in distilled water to obtain an aqueous phase. At another step, the polysorbate 80 and Span 60 are added into the aqueous phase and subjected to stirring, and the emtricitabine and the tenofovir are dissolved in the aqueous phase.

[0025] At another step, the aqueous phase is added to the homogeneous lipid mixture while stirring at a temperature of at least 60°C to obtain a mixture, and the mixture is emulsified using a high-shear homogenizer for at least 10-15 min to obtain a uniform dispersion. At another step, the uniform dispersion is subjected to ultrasonication using a probe sonicator for 10-20 min to reduce particle size and cooled to room temperature to solidify the lipid phase, thereby obtaining solid lipid nanoparticles. Further, at other step, the solid lipid nanoparticles are filtered through a 0.45 µm filter to remove larger particles and stored in a sealed container at a temperature of at least 4°C for stability.

[0026] Further, objects and advantages of the present invention will be apparent from a study of the following portion of the specification, the claims, and the attached drawings.
Detailed description of drawings:
[0027] The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate an embodiment of the invention, and, together with the description, explain the principles of the invention.

[0028] FIG. 1 illustrates a block diagram representing a composition for preparing solid lipid nanoparticles (SLNs) (100) for co-delivery of HIV antiretrovirals, in accordance to an exemplary embodiment of the invention.

[0029] FIG. 2 illustrates a graph representing a Fourier transform infrared spectroscopy results of emtricitabine and tenofovir, in accordance to an exemplary embodiment of the invention.

[0030] FIG. 3 illustrates a flowchart of a method for preparing the solid lipid nanoparticles for co-delivery of HIV antiretrovirals, comprising, in accordance to an exemplary embodiment of the invention.
Detailed invention disclosure:
[0031] Various embodiments of the present invention will be described in reference to the accompanying drawings. Wherever possible, same or similar reference numerals are used in the drawings and the description to refer to the same or like parts or steps.

[0032] The present disclosure has been made with a view towards solving the problem with the prior art described above, and it is an object of the present invention to provide a composition and method for preparing solid lipid nanoparticles 100 for co-delivery of HIV antiretrovirals such as emtricitabine and tenofovir, thereby enhancing therapeutic efficacy, stability, and bioavailability in the treatment of HIV infection.

[0033] According to an exemplary embodiment of the invention, FIG. 1 refers to a block diagram representing a composition for preparing solid lipid nanoparticles (SLNs) 100 for co-delivery of HIV antiretrovirals. The proposed solid lipid nanoparticles 100 encapsulate emtricitabine and tenofovir using a combination of lipids and surfactants, which ensures a controlled release of the drugs. The solid lipid nanoparticle 100 improves the solubility of antiretroviral drugs and extends their circulation time in the body.

[0034] The solid lipid nanoparticle 100 reduces the systemic toxicity associated with tenofovir by using a lipid matrix for controlled drug release and reduced peak plasma concentrations. The solid lipid nanoparticle ensures the drugs are homogeneously dispersed within the lipid matrix for effective co-delivery of both emtricitabine and tenofovir. The solid lipid nanoparticle 100 improves patient compliance by reducing the frequency of dosing through a controlled-release mechanism. The solid lipid nanoparticle addresses the challenges of poor drug absorption in HIV treatment, thereby ensuring efficient distribution to key viral reservoirs in the body.

[0035] In one embodiment herein, the composition comprises 45 to 47.2 weight percentage of stearic acid 102, 9 to 9.5 weight percentage of oleic acid 104, 4 to 4.8 weight percentage of polysorbate 80 (106), 4 to 4.8 weight percentage of Span 60 (108), 9 to 9.5 weight percentage of polyvinyl alcohol (PVA) 110, 15 to 19 weight percentage of polyethylene glycol (PEG) 112, 2 to 3 weight percentage of emtricitabine 114, and 2 to 3 weight percentage of tenofovir 116. The composition provides solid lipid nanoparticles 100 with enhanced bioavailability, stability, and controlled drug release of the emtricitabine 114 and the tenofovir 116. In one embodiment herein, the composition comprises 50 mg of the stearic acid 102, 10 mg of the oleic acid 104, 5 mg of the polysorbate 80 (106), 5 mg of the Span 60 (108), 10 mg of the polyvinyl alcohol (PVA) 110, 20 mg of the polyethylene glycol (PEG) 112, 3 mg of the emtricitabine 114, 3 mg of the tenofovir 116.

[0036] In one embodiment herein, the composition comprises 47. 16 weight percentage of the stearic acid 102, 9.43 weight percentage of the oleic acid 104, 4.7 weight percentage of the polysorbate 80 (106), 4.7 weight percentage of the Span 60 (108), 9.43 weight percentage of the polyvinyl alcohol (PVA) 110, 18.86 weight percentage of the polyethylene glycol (PEG) 112, 2.83 weight percentage of the emtricitabine 114, 2.83 weight percentage of the tenofovir 116.

[0037] In one embodiment herein, the stearic acid 102 obtains a solid lipid matrix to provide controlled release of the emtricitabine 114 and tenofovir 116. In one embodiment herein, the stearic acid 102 acts as the primary carrier of the active pharmaceutical ingredients (APIs), thereby ensuring their incorporation into the solid lipid matrix and facilitating controlled release over time. The choice of stearic acid as the solid lipid matrix is based on well-established properties of biocompatibility and the ability to form stable nanoparticles.

[0038] In one embodiment herein, the polysorbate 80 (106) and the span 60 (108) are used as surfactants to stabilize the solid lipid nanoparticles 100 and reduce particle size. In one embodiment herein, the polysorbate 80 (106) stabilizes the SLNs 100 by reducing the surface tension between the aqueous and lipid phases, which helps in maintaining a uniform particle size and preventing agglomeration. In one embodiment herein, the span 60 (108) enhances the overall stability of the formulation and contributes to reducing the particle size. The combination of the polysorbate 80 (106) and the span 60 (108) offers superior performance compared to conventional surfactants, thereby resulting in more stable solid lipid nanoparticles 100 with a uniform size distribution.

[0039] In one embodiment herein, the oleic acid 104 is used as a lipophilic enhancer to facilitate the incorporation and solubilization of the emtricitabine 114 and the tenofovir 116 within the solid lipid matrix. In one embodiment herein, the oleic acid 104 promotes the solubilization of the emtricitabine 114 and the tenofovir 116 within the solid lipid matrix, thereby ensuring efficient drug loading and release. This is critical for maintaining drug efficacy and ensuring that therapeutic levels of the drugs are delivered over an extended period. The combination of the stearic acid 102 and the oleic acid 104 creates a lipid environment that allows for optimal encapsulation of the APIs while maintaining the solid lipid nanoparticles 100 integrity.

[0040] In one embodiment herein, the polyvinyl alcohol (PVA) 110 is used as a stabilizer to maintain the solid lipid nanoparticle 100 stability during the formulation process and storage. In one embodiment herein, the PVA 110 helps to prevent particle aggregation by forming a protective coating around the solid lipid nanoparticles 100, thereby ensuring that the solid lipid nanoparticles 100 remain stable over time. This is particularly important for long-term storage, as it ensures the integrity and effectiveness of the formulation, even under varying conditions.

[0041] In one embodiment herein, the polyethylene glycol (PEG) 112 enhances the solubility and bioavailability of the emtricitabine 114 and the tenofovir 116 and improves the circulation time within the body. In one embodiment herein, the PEG 112 is configured to extend the circulation time of solid lipid nanoparticles 100 in the bloodstream by providing a hydrophilic surface, thereby reducing clearance by the reticuloendothelial system (RES). This allows for sustained drug release and better therapeutic outcomes. The presence of the PEG 112 in the formulation ensures that the solid lipid nanoparticles 100 can effectively deliver the emtricitabine 114 and the tenofovir 116 to their target sites while minimizing premature clearance from the body. In one embodiment herein, the solid lipid nanoparticles (SLNs) 100 are spherical in shape and have a particle size of approximately 100 nm which enhances drug absorption, and a zeta potential of at least ±25 mV. In one embodiment herein, the solid lipid nanoparticles (SLNs) 100 exhibit improved stability for long-term storage at a temperature of at least 4°C. The solid lipid nanoparticles (SLNs) 100 are evaluated for size, zeta potential, and drug release profile to ensure uniformity and performance.

[0042] According to an exemplary embodiment of the invention, FIG. 2 refers to a graph 200 representing a Fourier transform infrared (FTIR) spectroscopy results of the emtricitabine 114 and the tenofovir 116. The FTIR spectrum shows typical absorption patterns consistent with organic compounds, such as nucleoside and nucleotide analogs like the emtricitabine 114 and the tenofovir 116. The graph 200 comprises an X-axis and a Y-axis. The X-axis represents wavenumber (cm-1), indicating the frequency of the absorbed light. The Y-axis shows transmittance (%), which measures the amount of light that passes through the solid lipid nanoparticles 100.

[0043] In one embodiment herein, the graph 200 exhibits a broad peak (3418.20 cm⁻¹) that corresponds to O-H stretching vibrations, which are consistent with hydroxyl groups present in the tenofovir 116 (as part of its phosphonic acid group) and the emtricitabine 114 (in its hydroxyl-containing sugar moiety). In one embodiment herein, the graph 200 exhibits sharp peaks (2912.00, 2851.84 cm⁻¹), which are indicative of C-H stretching vibrations from alkyl groups. Both the emtricitabine 114 and the tenofovir 116 contain aliphatic and cyclic components that exhibit such C-H vibrations.

[0044] In one embodiment herein, the graph 200 exhibits a strong peak (1693.23 cm⁻¹). The strong peak at this wavenumber suggests the presence of a carbonyl (C=O) group. In the tenofovir 116, this could correspond to the carbonyl group within its structure, while in the emtricitabine 114, this may arise from specific functional groups contributing to similar vibrational modes. In one embodiment herein, the graph 200 exhibits complex peaks in the fingerprint region (1500-1000 cm⁻¹). This fingerprint region shows multiple peaks associated with C-O, C-N, and possibly P=O stretching vibrations. The tenofovir 116 contains a phosphonic acid group, like P=O and P-O bonds contribute to this region. In one embodiment herein, the emtricitabine 114 includes C-O and C-N bonds within its nucleoside structure, which also exhibit vibrations in this range.

[0045] In one embodiment herein, the broad O-H peak and the complex fingerprint region align with the functional groups in the tenofovir 114, like hydroxyl and phosphonic acid functionalities. These features confirm status as nucleotide analog with significant hydrophilic properties. In one embodiment herein, the observed peaks in the fingerprint region and the broad O-H stretch, correspond well to the hydroxyl groups and the aromatic features of emtricitabine's cytosine-like nucleoside structure. The observed spectral features not only confirm the presence of key functional groups in the emtricitabine 114 and tenofovir 116 but also highlight their potential to form hydrogen bonds and interact with biological targets such as viral enzymes. The above results show a combination of both drug purity and compatibility.

[0046] According to an exemplary embodiment of the invention, FIG. 3 refers to a flowchart 300 of a method for preparing solid lipid nanoparticles for co-delivery of HIV antiretrovirals. At step 302, the stearic acid 102 is melted at a temperature of at least 60°C to obtain a lipid phase. At step 304, the oleic acid 104 is added to the melted stearic acid 102 to obtain a homogeneous lipid mixture. At step 306, the polyvinyl alcohol (PVA) 110 and the polyethylene glycol (PEG) 112 are dissolved in distilled water to obtain an aqueous phase.

[0047] At step 308, the polysorbate 80 (106) and the Span 60 (108) are added into the aqueous phase and subjected to stirring, and the emtricitabine 114 and the tenofovir 116 are dissolved in the aqueous phase. At step 310, the aqueous phase is added to the homogeneous lipid mixture while stirring at a temperature of at least 60°C to obtain a mixture and the mixture is emulsified using a high-shear homogenizer for at least 10-15 min to obtain a uniform dispersion. At step 312, the uniform dispersion is subjected to ultrasonication using a probe sonicator for at least 10-20 min to reduce particle size and cooled to room temperature to solidify the lipid phase, thereby obtaining solid lipid nanoparticles 100. Further, at step 314, the solid lipid nanoparticles 100 are filtered through a 0.45 µm filter to remove larger particles and stored in a sealed container at a temperature of at least 4°C for stability.

[0048] Numerous advantages of the present disclosure may be apparent from the discussion above. In accordance with the present disclosure, a composition for preparing solid lipid nanoparticles (SLNs) is disclosed. The proposed invention provides a composition and method for preparing solid lipid nanoparticles 100 for co-delivery of HIV antiretrovirals such as emtricitabine and tenofovir, thereby enhancing therapeutic efficacy, stability, and bioavailability in the treatment of HIV infection.

[0049] The proposed solid lipid nanoparticles 100 encapsulate emtricitabine and tenofovir using a combination of lipids and surfactants, which ensures a controlled release of the drugs. The solid lipid nanoparticle 100 improves the solubility of antiretroviral drugs and extends their circulation time in the body. The solid lipid nanoparticle 100 reduces the systemic toxicity associated with tenofovir by using a lipid matrix for controlled drug release and reduced peak plasma concentrations. The solid lipid nanoparticle 100 ensures the drugs are homogeneously dispersed within the lipid matrix for effective co-delivery of both emtricitabine and tenofovir. The solid lipid nanoparticle 100 improves patient compliance by reducing the frequency of dosing through a controlled-release mechanism.

[0050] The solid lipid nanoparticle 100 utilizes oleic acid to enhance the solubilization of emtricitabine and tenofovir within the lipid matrix. The solid lipid nanoparticle 100 addresses the challenges of poor drug absorption in HIV treatment, thereby ensuring efficient distribution to key viral reservoirs in the body. The solid lipid nanoparticle 100 utilizes stearic acid as a solid lipid matrix for a controlled and sustained release of the active pharmaceutical ingredients (APIs).

[0051] It will readily be apparent that numerous modifications and alterations can be made to the processes described in the foregoing examples without departing from the principles underlying the invention, and all such modifications and alterations are intended to be embraced by this application.
, Claims:CLAIMS:
I/We Claim:
1. A composition for preparing solid lipid nanoparticles (SLNs) (100) for co-delivery of HIV antiretrovirals, comprising:
45 to 47.2 weight percentage of stearic acid (102);
9 to 9.5 weight percentage of oleic acid (104);
4 to 4.8 weight percentage of polysorbate 80 (106);
4 to 4.8 weight percentage of Span 60 (108);
9 to 9.5 weight percentage of polyvinyl alcohol (PVA) (110);
15 to 19 weight percentage of polyethylene glycol (PEG) (112);
2 to 3 weight percentage of emtricitabine (114); and
2 to 3 weight percentage of tenofovir (116),
whereby the composition provides solid lipid nanoparticles (100) with enhanced bioavailability, stability, and controlled drug release of the emtricitabine (114) and the tenofovir (116).
2. The composition as claimed in claim 1, wherein the stearic acid (102) obtains a solid lipid matrix to provide controlled release of the emtricitabine (114) and the tenofovir (116).
3. The composition as claimed in claim 1, wherein the polysorbate 80 (106) and the Span 60 (108) are used as surfactants to stabilize the solid lipid nanoparticles and reduce particle size.
4. The composition as claimed in claim 1, wherein the oleic acid (104) is used as a lipophilic enhancer to facilitate the incorporation and solubilization of the emtricitabine (114) and the tenofovir (116) within the solid lipid matrix.
5. The composition as claimed in claim 1, wherein the polyvinyl alcohol (PVA) (110) is used as a stabilizer to maintain solid lipid nanoparticle stability during the formulation process and storage.
6. The composition as claimed in claim 1, wherein the polyethylene glycol (PEG) (112) enhances the solubility and bioavailability of the emtricitabine (114) and the tenofovir (116) and improves the circulation time within the body.
7. The composition as claimed in claim 1, wherein the solid lipid nanoparticles (SLNs) (100) are spherical in shape and have a particle size of approximately 100 nm which enhances drug absorption, and a zeta potential of at least ±25 mV.
8. The composition as claimed in claim 1, wherein the solid lipid nanoparticles (SLNs) (100) exhibit improved stability for long-term storage at a temperature of at least 4°C.
9. The composition as claimed in claim 1, wherein the solid lipid nanoparticles (SLNs) (100) are evaluated for size, zeta potential, and drug release profile to ensure uniformity and performance.
10. A method for preparing solid lipid nanoparticles for co-delivery of HIV antiretrovirals, comprising:
melting stearic acid (102) at a temperature of at least 60°C to obtain a lipid phase;
adding oleic acid (104) to the lipid phase (102) to obtain a homogeneous lipid mixture;
dissolving polyvinyl alcohol (PVA) (110) and polyethylene glycol (PEG) (112) in distilled water to obtain an aqueous phase;
adding polysorbate 80 (106) and Span 60 (108) into the aqueous phase and subjected to stirring, and dissolving emtricitabine (114) and tenofovir (116) in the aqueous phase;
adding the aqueous phase to the homogeneous lipid mixture while stirring at a temperature of at least 60°C to obtain a mixture and emulsifying the mixture using a high-shear homogenizer for at least 10-15 min to obtain a uniform dispersion;
subjecting the uniform dispersion to ultrasonication using a probe sonicator for at least 10-20 min to reduce particle size and cooling the uniform dispersion to room temperature to solidify the lipid phase, thereby obtaining solid lipid nanoparticles (100); and
filtering the solid lipid nanoparticles (100) through a 0.45 µm filter to remove larger particles and storing the solid lipid nanoparticles (100) in a sealed container at a temperature of at least 4°C for stability.

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