Fabrication and Preliminary Assessment of Neem Fruit Mucilage as Mucoadhesive Abetting Assets with Methpol-934P for Acyclovir Delivery from Mucoadhesive Microcapsules

In this study, we investigated the mucoadhesive properties of neem fruit mucilage by incorporating it into mucoadhesive microcapsules with Acyclovir (ACR). Methpol-934P and Neem fruit mucilage (NFM) was used to construct 12 different mucoadhesive microcapsules. We assessed FTIR and DSC capabilities for compatibility with ACR and NFM. ACR mucoadhesive microcapsules (ANMM) were characterized for mucoadhesion and ACR release Physico-chemical characteristics. CR was found to be compatible with NFM in the research. The entrapment increased as the levels of NFM in the formulations increased, and mucoadhesion time was longer in formulations with higher levels of NFM. As levels of NFM increase in formulations, the release of drugs is slightly reduced. NFM may be responsible for this due to its release retarding properties. An additive of neem fruit mucilage allowed for the retention of ACR after ingestion when a mucoadhesive polymer (methpol 934P) was used.

A unique attitude is emerging for drug administration to increase the gastric availability of drugs with patient consent. Among the various dosage forms, gastro retentive microcapsules are of special concern as they can be easily prepared and administered 1,2 .
Herpes simplex, herpes zoster, and chicken pox are all contagions treated with acyclovir, a purine nucleoside analogue 3,4 . Approximately 15-30% of Acyclovir is bioavailable orally. Acyclovir has a half-life 5 of ~2 h. After giving the medication orally, the medication is well absorbed into the stomach.
A mucoadhesive system's effectiveness is significantly affected by the polymer used. Many patients prefer oral drug administration due to its convenience. Many polymers have been tried for mucoadhesive drives, which are rare and expensive. An ideal polymer would aid mucoadhesion and be derived from nature. The authors plan to examine mucoadhesive microcapsules using neem fruit mucilage (NFM). The antiviral properties of NFM have been demonstrated in studies 6,7 . NFM may be helpful in antiviral therapy. In expanded time, ANMM aims to achieve steady-state availability. As they are designed for ease, precision liberation systems are an effective solution for short-acting drugs and those that require incessant medicating.

extraction of mucilage
Depletion of expression was defined 8 by Ahad et al., 2021. After washing and removing the outer layer of the neem fruits, they were soaked in water, boiled for an hour, and cooled. The seeds were separated by using ethyl acetate, butanol, and petroleum ether (50%). Using a multilayered muslin cloth bag, the marc was extracted from the mucilage. The mucilage was parted, parched in an oven (ACM-22066) at 40°C, poised, ground, allowed to pass over a # 80 sieve (MSW Labs) and stored in a desiccator (Tarson 402020) at 30°C and 45% RH.

Preparation of anMM
Dichloromethane and acetic acid (2% v/v) were used in the blending of Methpol 934P, ACR, EC, and NFM. Continuous stirring of this mixture into liquid paraffin (containing span 80) was achieved using a three-bladed propeller stirrer (IKA-R1381). We added glutaraldehyde at a rate of 4 drops per minute dropwise to the sample as part of this procedure. Three hours of stirring followed. To remove liquid paraffin, the Acyclovir-Neem mucoadhesive microcapsules (ANMM) were centrifuged and washed with petroleum ether. For the removal of residual glutaraldehyde, an ANMM was suspended in a 5% sodium bisulfite solution for 15 min. After washing with distilled water, the last step was to dry the clothes. Desiccators were used to dry and store the ANMM 10-12 . evaluation parameters drug excipient compatibility studies dsC studies In a mini pan of DSC, ACR and NFM were mixed in a 1:1 ratio (10 mg) and scanned from 50 to 300°C (Venchal Scientific-412105-USA).

Ftir studies
ACR and NFM were examined using FTIR spectroscopy (Bruker) by scanning at a 4000-400 cm "1 array. evaluation of physical properties Measurement of particle size ANMM particles were measured using a stage micrometer. Dry ANMM were measured with an eyepiece micrometre on a hygienic glass slide 13 . At least 100 ANMM were counted per batch.

Production yield
In each of the three trials, the average weight of parched ANMM (W 1 ) recovered from each trial was compared 14 to the total of the initial dry weight (W 2 ).

Entrapment Efficiency
100 mg of ANMM were dispersed in 0.1 M HCl overnight with erratic quivering. The mixture was filtered at 254 nm, and the filtrate was analyzed spectrophotometrically (Elico Spectrophotometer, SL-174). An evaluation of entrapment efficiency was based on the ratio between the actual amount of drug in the formulation and the amount initially added 15 .

Measurement of swelling
An HCl solution of 0.1M was used to swell ANMM. As determined from the following equation 16 , the weight gain was determined by the difference between the weight gained at time t (Xt) and the beginning time (t = 0 [X0]).
Where Xt-weight of the ANMM after time t; Xo-Initial weight of the ANMM

Mucoadhesion Measurement study
It was determined that the mucoadhesive time (MT) of a fresh 5 cm piece of sheep stomach gained from a local slaughterhouse within 60 min of the animal's death and eviscerated by washing with isotonic saline. The mucosal surface was weighed using ANMM and a polyethene plate at a position of 40° relative to the straight line, which was stationary. Infuse HCl (0.1M) at 37±0.5°C at a rate of 5 ml/min, simulating 37±0.5°C. By visual inspection, we measured how long it takes to remove all ANMM from the mucosal surface of the sheep's stomach [17][18][19] .

In Vitro aCr release study
As a dissolution medium, 900 ml of HCl (0.1N HCl) was used in the USP-II apparatus at a stirring rate of 50±5 rpm at a temperature of 37±0.5°C. At different breaks, a 5 ml sample was introverted, and the dissolution media were replenished. Spectrophotometric measurements were then performed at 254nm on the samples 20-23 .

results and disCussion
In addition to evaluating the congeniality of the fresh NFM, its colour was yellowish green, which assists ANMM.

Compatibility studies
Based on the DSC assessment, the pure ACR produced a sharp endothermic peak, indicating its purity. Combining this peak with leftshifting excipients broadens it. DSC observations indicate that ACR does not interact with the excipients.
The ACR pure-form spectrum exhibits FTIR bands for secondary amines, phenyl esters, and carboxylic groups. Blend (F-5) had peaks and stretches like pure drugs. Excipients did not obstruct peaks or stretches of the spectrum of ACR.

Physical properties Particle size
Optical microscopy was used to fix particle size for all formulations. ANMM array sizes range from 33.92±0.7 to 39.6±0.8 µm ( Figure  1), with F-8 having the largest particle size.

in vitro drug release
Analyses were conducted to determine whether ANMM dissolves. As NFM shows more binding properties and releases retarding properties, formulations with 50 to 100 mg of NFM show good drug release, whereas formulations with F-5 to F-12 show suppressed drug release.

swelling Measurement
By analyzing the pattern of ACR release, the ANMM can be used to determine the extent of mucoadhesion. When preparing any mucoadhesive formulation, this study should be considered. Different concentrations of NFM were tested on the swelling indices of the ANMM. The swelling index dropped steadily as the concentration of NFM decreased, and batch F-12 was the most swollen. Several polar compounds are present in NFM, which enable it to absorb and hold water, as well as have swelling assets.

% drug entrapment
Entrapment of ANMM ranged from 65.9±1.27 to 79.6±0.98 and formulations with 125mg of NFM gave good entrapment of ACR ( Figure 2). in vitro mucoadhesion time All batches of ANMM had mucoadhesions ranging from 9.2±0.08g (F-1) to 12.4±0.16g (F-12) (Figure 3). The mucoadhesion time was considered to increase with a higher NFM content and higher levels of methpol 934 P.

aCr estimation
A UV-VIS spectrometer was used to obtain a calibration curve for ACR estimation in 0.1M HCl solution at 254 nm ë max . According to Beer's law, the calibration curve ranged from 0-10 µg/ml (repeated three times). Such data can be used to determine the uniformity of content.

ConClusion
Acyclovir (ACR) is released from mucoadhesive polymers at a rate and quantity controlled by the polymers. The ACR is released from the stomach after the microcapsules are digested. To formulate ACR, Neem (Azadirachta indica) fruit mucilage (NFM) combined with methpol 934 P was used. NFM was proven to have antiviral activity in addition to mucoadhesive assets. As earlier studied by Shiraki et al., 2021. Compared to other formulations, F-2 to F-4 with fewer NFM (50 to 100 mg) has more entrapped ACR in addition to the mucoadhesion. An additional increase in NFM retards the ACR release and shows sustained release unlike it was observed by Ghumman et al., 2020. Using the results of this study, it can be concluded that the mucoadhesive microcapsules of ACR with NFM aided by methpol 934 P are an effective way to retain the stomach and support increased bioavailability.

aCknowledgeMent
The authors feel privileged to thank the department of pharmacy, Annamalai University, Annamalai Nagar, Tamil Nadu, India for their support and encouragement.

Conflict of Interests
The authors declare no conflict of interest.

Funding sources
There is no funding source.